The number and activity of brown adipocytes are linked to the ability of mammals to resist body fat accumulation. In some conditions, certain white adipose tissue (WAT) depots are readily convertible to a ''brown-like'' state, which is associated with weight loss. Irisin, a newly identified hormone, is secreted by skeletal muscles into circulation and promotes WAT "browning" with unknown mechanisms. In the current study, we demonstrated in mice that recombinant irisin decreased the body weight and improved glucose homeostasis. We further showed that irisin upregulated uncoupling protein-1 (UCP-1; a regulator of thermogenic capability of brown fat) expression. This effect was possibly mediated by irisin-induced phosphorylation of the p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-related kinase (ERK) signaling pathways. Inhibition of the p38 MAPK by SB203580 and ERK by U0126 abolished the upregulatory effect of irisin on UCP-1. In addition, irisin also promoted the expression of betatrophin, another newly identified hormone that promotes pancreatic b-cell proliferation and improves glucose tolerance. In summary, our data suggest that irisin can potentially prevent obesity and associated type 2 diabetes by stimulating expression of WAT browning-specific genes via the p38 MAPK and ERK pathways.

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Self-healing, adhesive conductive hydrogels are of great significance in wearable electronic devices, flexible printable electronics, and tissue engineering scaffolds. However, designing self-healing hydrogels with multifunctional properties such as high conductivity, excellent mechanical property, and high sensitivity remains a challenge. In this work, the conductive self-healing nanocomposite hydrogels based on nanoclay (laponite), multiwalled carbon nanotubes (CNTs), and N-isopropyl acrylamide are presented. The presented nanocomposite hydrogels displayed good electrical conductivity, rapid self-healing and adhesive properties, flexible and stretchable mechanical properties, and high sensitivity to near-infrared light and temperature. These excellent properties of the hydrogels are demonstrated by the three-dimensional (3D) bulky pressure-dependent device, human activity monitoring device, and 3D printed gridding scaffolds. Good cytocompatibility of the conductive hydrogels was also evaluated with L929 fibroblast cells. These nanocomposite hydrogels have great potential for applications in stimuli-responsive electrical devices, wearable electronics, and so on.

We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual-guide RNAs in three cell lines, altogether comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified and these patterns replicated with combinatorial drugs at 75% precision. Based on these results we anticipate cellular context will be critical to synthetic-lethal therapies.

There is a need in molecular biology and biomedical research for open-ended, hypothesis-generating research, in order to discover previously unknown molecular mechanisms. Genetic screening provides a powerful approach for identifying genes, pathways and mechanisms involved in a given phenotype or biological process. This is illustrated by the many successes of forward genetics in cell lines 1 and in model organisms such as flies 2,3 , worms 4 , yeast 5 , plants 6 and fish 7 , and pioneering work in RNA interference (RNAi) screens 8,9 .CRISPR screens exploit the efficiency and flexibility of CRISPR-Cas genome editing 10 . They have become a popular and productive tool for biological discovery in a broad range of applications 11,12 . In a typical pooled CRISPR screen (FIg. 1), a CRISPR guide RNA (gRNA) library is introduced in bulk into cells, such that individual cells receive different gRNAs and are perturbed according to the gRNA received by the cell. These gRNAs are usually delivered by lentiviral transduction and are integrated into the DNA of the target cells, making it possible to efficiently determine the induced perturbations based on the gRNA sequence.