A variety of extracellular signals are transduced across the cell membrane by the enzyme phosphoinositide-specific phospholipase C-beta (PLC-beta) coupled with guanine-nucleotide-binding G proteins. There are four isoenzymes of PLC-beta, beta1-beta4, but their functions in vivo are not known. Here we investigate the role of PLC-beta1 and PLC-beta4 in the brain by generating null mutations in mice: we found that PLCbeta1-/- mice developed epilepsy and PLCbeta4-/- mice showed ataxia. We determined the molecular basis of these phenotypes and show that PLC-beta1 is involved in signal transduction in the cerebral cortex and hippocampus by coupling predominantly to the muscarinic acetylcholine receptor, whereas PLC-beta4 works through the metabotropic glutamate receptor in the cerebellum, illustrating how PLC-beta isoenzymes are used to generate different functions in the brain.

Intracellular thermometry at the microscopic level is currently a hot topic. Herein we describe a small molecule fluorescent thermometer targeting mitochondria (Mito thermo yellow). Mito thermo yellow successfully demonstrates the ability to monitor the intracellular temperature gradient, generated by exogenous heating, in various cells.

Drug toxicity is a long-standing concern of modern medicine. A typical anti-pain/fever drug paracetamol often causes hepatotoxicity due to peroxynitrite ONOO . Conventional blood tests fail to offer real-time unambiguous visualization of such hepatotoxicity in vivo. Here we report a luminescent approach to evaluate acute hepatotoxicity in vivo by chromophore-conjugated upconversion nanoparticles. Upon injection, these nanoprobes mainly accumulate in the liver and the luminescence of nanoparticles remains suppressed owing to energy transfer to the chromophore. ONOO can readily bleach the chromophore and thus recover the luminescence, the presence of ONOO in the liver leads to fast restoring of the near-infrared emission. Taking advantages of the high tissue-penetration capability of near-infrared excitation/emission, these nanoprobes achieve real-time monitoring of hepatotoxicity in living animals, thereby providing a convenient screening strategy for assessing hepatotoxicity of synthetic drugs.

The rapid and sensitive classification of bacteria is the first step of bacterial community researchand the treatment of infection. Herein, afluorescent probe BacGO is presented, which shows the best universal selectivity for Gram-positive bacteria among knownp robes with am inimum staining procedure for sample detection and enrichment of the live bacteria. BacGO could also be used to assess of the Gram status in the bacterial community from wastewater sludge. Furthermore, BacGO could sensitively and selectively detect aG ram-positive bacterial infection, not only in vitro but also using an in vivo keratitis mouse model. BacGO provides an unprecedented researchtool for the study of dynamic bacterial communities and for clinical application.

Cellular reprogramming suffers from low efficiency especially for the human cells. To deconstruct the heterogeneity and unravel the mechanisms for successful reprogramming, we adopted single-cell RNA sequencing (scRNA-Seq) and single-cell assay for transposase-accessible chromatin (scATAC-Seq) to profile reprogramming cells across various time points. Our analysis revealed that reprogramming cells proceed in an asynchronous trajectory and diversify into heterogeneous subpopulations. We identified fluorescent probes and surface markers to enrich for the early reprogrammed human cells. Furthermore, combinatory usage of the surface markers enabled the fine segregation of the early-intermediate cells with diverse reprogramming propensities. scATAC-Seq analysis further uncovered the genomic partitions and transcription factors responsible for the regulatory phasing of reprogramming process. Binary choice between a FOSL1 and a TEAD4-centric regulatory network determines the outcome of a successful reprogramming. Together, our study illuminates the multitude of diverse routes transversed by individual reprogramming cells and presents an integrative roadmap for identifying the mechanistic part list of the reprogramming machinery.

The cell‐by date: The fluorescent compound CDy1 selectively stains embryonic stem cells (see scheme). CDy1 was used to identify fibroblasts undergoing reprogramming to induced pluripotent stem cells prior to the expression of green fluorescent protein under the control of the Oct4 promoter.

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