AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis, which coordinates metabolic pathways and thus balances nutrient supply with energy demand. Because of the favorable physiological outcomes of AMPK activation on metabolism, AMPK has been considered to be an important therapeutic target for controlling human diseases including metabolic syndrome and cancer. Thus, activators of AMPK may have potential as novel therapeutics for these diseases. In this review, we provide a comprehensive summary of both indirect and direct AMPK activators and their modes of action in relation to the structure of AMPK. We discuss the functional differences among isoform-specific AMPK complexes and their significance regarding the development of novel AMPK activators and the potential for combining different AMPK activators in the treatment of human disease.

Graphical Abstract Highlights d Symbiont-generated lactate is critical for Lgr5 + ISC-mediated epithelial development d Lactate signals through the G-protein-coupled receptor Gpr81 to elicit ISC proliferation d Lactobacillus plantarum lacking lactate dehydrogenase fails to induce ISC regeneration d Pre-feeding of lactate protects mice from chemotherapy-and radiation-induced gut damage In Brief Lee et al. reveal how lactic-acidproducing bacteria, including Bifidobacterium and Lactobacillus spp., support intestinal epithelial cell regeneration. Symbiont-derived lactate is sensed by G-protein-coupled receptor 81 on Paneth and stromal cells to promote regeneration in a Wnt3/ b-catenindependent manner. Lactate preadministration protects mice exposed to radiation-and chemotherapy-induced intestinal damage. SUMMARY Symbionts play an indispensable role in gut homeostasis, but underlying mechanisms remain elusive. To clarify the role of lactic-acid-producing bacteria (LAB) on intestinal stem-cell (ISC)-mediated epithelial development, we fed mice with LAB-type symbionts such as Bifidobacterium and Lactobacillus spp. Here we show that administration of LAB-type symbionts significantly increased expansion of ISCs, Paneth cells, and goblet cells. Lactate stimulated ISC proliferation through Wnt/b-catenin signals of Paneth cells and intestinal stromal cells. Moreover, Lactobacillus plantarum strains lacking lactate dehydrogenase activity, which are deficient in lactate production, elicited less ISC proliferation. Pre-treatment with LAB-type symbionts or lactate protected mice in response to gut injury provoked by combined treatments with radiation and a chemotherapy drug. Impaired ISC-mediated epithelial development was found in mice deficient of the lactate G-proteincoupled receptor, Gpr81. Our results demonstrate that LAB-type symbiont-derived lactate plays a pivotal role in promoting ISC-mediated epithelial development in a Gpr81-dependent manner.

Metagenomic studies show that diverse resident viruses inhabit the healthy gut; however, little is known about the role of these viruses in the maintenance of gut homeostasis. We found that mice treated with antiviral cocktail displayed more severe dextran sulfate sodium (DSS)-induced colitis compared with untreated mice. DSS-induced colitis was associated with altered enteric viral abundance and composition. When wild-type mice were reconstituted with Toll-like receptor 3 (TLR3) or TLR7 agonists or inactivated rotavirus, colitis symptoms were significantly ameliorated. Mice deficient in both TLR3 and TLR7 were more susceptible to DSS-induced experimental colitis. In humans, combined TLR3 and TLR7 genetic variations significantly influenced the severity of ulcerative colitis. Plasmacytoid dendritic cells isolated from inflamed mouse colon produced interferon-β in a TLR3 and TLR7-dependent manner. These results imply that recognition of resident viruses by TLR3 and TLR7 is required for protective immunity during gut inflammation.

The dynamic processing of optoelectronic signals carrying temporal and sequential information is critical to various machine learning applications including language processing and computer vision. Despite extensive efforts to emulate the visual cortex of human brain, large energy/time overhead and extra hardware costs are incurred by the physically separated sensing, memory, and processing units. The challenge is further intensified by the tedious training of conventional recurrent neural networks for edge deployment. Here, we report in-sensor reservoir computing for language learning. High dimensionality, nonlinearity, and fading memory for the in-sensor reservoir were achieved via two-dimensional memristors based on tin sulfide (SnS), uniquely having dual-type defect states associated with Sn and S vacancies. Our in-sensor reservoir computing demonstrates an accuracy of 91% to classify short sentences of language, thus shedding light on a low training cost and the real-time solution for processing temporal and sequential signals for machine learning applications at the edge.

The integration of efficient, miniaturized group IV lasers into CMOS architecture holds the key to the realization of fully functional photonic-integrated circuits. Despite several years of progress, however, all group IV lasers reported to date exhibit impractically high thresholds owing to their unfavourable bandstructures. Highly strained germanium with its fundamentally altered bandstructure has emerged as a potential low-threshold gain medium, but there has yet to be a successful demonstration of lasing from this seemingly promising material system. Here we demonstrate a low-threshold, compact group IV laser that employs a germanium nanowire under a 1.6% uniaxial tensile strain as the gain medium. The amplified material gain in strained germanium can sufficiently overcome optical losses at 83 K, thus allowing the observation of multimode lasing with an optical pumping threshold density of ~3.0 kW cm−2. Our demonstration opens new possibilities for group IV lasers for photonic-integrated circuits.

Sodium carboxymethylcellulose, an etherified derivative of cellulose, has been found to realize stable aqueous dispersion of single-wall carbon nanotubes (SWNTs) that is twenty times more concentrated than when a surfactant is used under the same condition. The dispersion as well as thin films prepared from it exhibits well-resolved near-infrared photoluminescence peaks originating from band-gap transitions in semiconducting SWNTs, a sign of isolated individual tubes. Mechanical stretching of the film strongly aligns the tubes, as demonstrated by considerable dichroism in their absorption spectra. Possessing high optical quality and uniformity, these densely dispersed SWNT films are expected to serve as an important platform for SWNTs’ optical, electrical, and optoelectronic applications, especially because cellulose derivatives are cheap, mass-produced, safe, water-processable, and environmentally benign.

The Langmuir-Blodgett technique has been applied to build optically homogeneous thin films of chemically solubilized single-wall carbon nanotubes (s-SWNTs) which possess good surface spreading properties at the air/water interface. Deposition can be performed in a layer-by-layer fashion up to 100 or more layers either by horizontal lifting or vertical dipping, allowing to readily control the film thickness. Their visible to near-infrared absorption spectra showing the characteristic features of semiconducting and metallic SWNTs prove the intactness of their one-dimensional electronic states during the preparation process. Polarized absorption spectroscopy and atomic force microscope (AFM) observation demonstrate that the tubes are oriented in the direction of the trough barrier (horizontal lifting) or in the dipping direction (vertical dipping). These are attributed to compression-induced or flow-induced orientation, respectively, the latter found to be much stronger than the former. The realization of homogeneous thin films of SWNTs with a controllable thickness and tube orientation should be an important basis for the future development of their scientific understanding and technological applications.

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