SUMMARY Intracellular microRNAs (miRNAs) are key regulators of gene expression. The role of extracellular miRNAs in neuronal activation and sensory behaviors are unknown. Here we report an unconventional role of extracellular miRNAs for rapid excitation of nociceptor neurons via toll-like receptor-7 (TLR7) and its coupling to TRPA1 ion channel. miRNA-let-7b induces rapid inward currents and action potentials in dorsal root ganglion (DRG) neurons. These responses require the GUUGUGU motif, only occur in neurons co-expressing TLR7 and TRPA1, and are abolished in mice lacking Tlr7 or Trpa1. Furthermore, let-7b induces TLR7/TRPA1-dependent single channel activities in DRG neurons and HEK293 cells over-expressing TLR7/TRPA1. Intraplantar injection of let-7b elicits rapid spontaneous pain via TLR7 and TRPA1. Finally, let-7b can be released from DRG neurons by neuronal activation, and let-7b inhibitor reduces formalin-induced TRPA1 currents and spontaneous pain. Thus, secreted extracellular miRNAs may serve as novelpain mediatorsvia activating TLR7 /TRPA1in nociceptor neurons.

Lithium-ion batteries have dominated the high performance and mobile market for last decade. Despite their dominance in many areas, the development of current commercial lithium-ion batteries is experiencing bottlenecks, limited by safety risks such as: leakage, burning, and even explosions due to the low-boiling point organic liquid electrolytes. Solid electrolyte is a promising option to solve or mitigate those issues. Among all solid electrolytes, polymer based solid electrolytes have the advantages of low flammability, good flexibility, excellent thermal stability, and high safety. Numerous researchers have focused on implementing solid polymer based Li-ion batteries with high performance. Nevertheless, low Li-ion conductivity and poor mechanical properties are still the main challenges in its commercial development. In order to tackle the issues and improve the overall performance, composites with external particles are widely investigated to form a polymer-based composite electrolyte. In light of their work, this review discusses the progress of polymer-based composite lithium ion's solid electrolytes. In particular, the structures, ionic conductivities, electrochemical/chemical stabilities, and fabrications of solid polymer electrolytes are introduced in the text and summarized at the end. On the basis of previous work, the perspectives of solid polymer electrolytes are provided especially toward the future of lithium ion batteries.

A general dealloying strategy is developed to prepare multi-component alloys with high thermal stability, electrochemical durability, and catalytic activity.

Ir‐based binary and ternary alloys are effective catalysts for the electrochemical oxygen evolution reaction (OER) in acidic solutions. Nevertheless, decreasing the Ir content to less than 50 at% while maintaining or even enhancing the overall electrocatalytic activity and durability remains a grand challenge. Herein, by dealloying predesigned Al‐based precursor alloys, it is possible to controllably incorporate Ir with another four metal elements into one single nanostructured phase with merely ≈20 at% Ir. The obtained nanoporous quinary alloys, i.e., nanoporous high‐entropy alloys (np‐HEAs) provide infinite possibilities for tuning alloy's electronic properties and maximizing catalytic activities owing to the endless element combinations. Particularly, a record‐high OER activity is found for a quinary AlNiCoIrMo np‐HEA. Forming HEAs also greatly enhances the structural and catalytic durability regardless of the alloy compositions. With the advantages of low Ir loading and high activity, these np‐HEA catalysts are very promising and suitable for activity tailoring/maximization.

Developing highly efficient catalysts for oxygen evolution reactions (OER) is a key step for rechargeable metal− oxygen batteries and water splitting. Usually, binary NiFe or ternary NiCoFe nano-alloys are used as the OER catalysts. Herein, combining the precursor alloy design with chemical etching, a simple dealloying route is developed to controllably incorporate five or more nonprecious metals into one nanostructured alloy with a naturally oxidized surface, that is, nanoporous high entropy alloys (np-HEAs) covered with high-entropy (oxy)hydroxides (HEOs). It is found that the alloy composition plays a dominant role in the OER activity enhancement with the np-AlNiCoFeX (X = Mo, Nb, Cr) combination showing the highest activity. Forming quinary HEAs also greatly enhances the electrochemical cycling stabilities compared with the ternary and quaternary counterparts. The result indicates the significance of synergistically incorporating five or more metal elements in one single-phase nanostructure, which provides more structural and chemical degrees of freedom to boost the catalytic performance, overcoming the restriction of normal binary or ternary alloys. Multinary transition metal-based np-HEA is a new class of promising catalyst for various important reactions.

Hepatic fibrosis is the common wound-healing response to chronic liver injury. In this process, activation of hepatic stellate cells is characteristic of cell proliferation and migration, production of collagen and other extracellular matrix (ECM) molecules, and contraction after transforming into myofibroblasts. It has been shown that the fibrogenic process is prominently regulated by transforming growth factor-beta1 (TGF-beta1) and that the specific blockade of TGF-beta1/Smad3 signaling may therapeutically intervene the fibrosis of various tissues. In this review, we attempt to integrate recent advances in the understanding of the mechanisms underlying TGF-beta1/Smad3 pathway modulation of ECM gene expression in the context of liver fibrosis, discuss intervention strategies targeting the blockade of related signal pathways, and look into novel ways to the safe and efficacious prevention and treatment of hepatic fibrosis.

Although itch sensation is an important protective mechanism for animals, chronic itch remains a challenging clinical problem. Itch processing has been studied extensively at the spinal level. However, how itch information is transmitted to the brain and what central circuits underlie the itch-induced scratching behavior remain largely unknown. We found that the spinoparabrachial pathway was activated during itch processing and that optogenetic suppression of this pathway impaired itch-induced scratching behaviors. Itch-mediating spinal neurons, which express the gastrin-releasing peptide receptor, are disynaptically connected to the parabrachial nucleus via glutamatergic spinal projection neurons. Blockade of synaptic output of glutamatergic neurons in the parabrachial nucleus suppressed pruritogen-induced scratching behavior. Thus, our studies reveal a central neural circuit that is critical for itch signal processing.

No abstract