Alzheimer's disease (AD) is a neurodegenerative disorder that causes progressive memory and cognitive decline due to the selective neuronal loss in the cortex and hippocampus of the brains. Generation of human induced pluoripotent stem (hiPS) cells holds great promise for disease modeling and drug discovery in AD. In this study, we used neurons with forebrain marker expression from two unrelated hiPS cell lines. As both populations of neurons were vulnerable to β-amyloid 1-42 (Aβ1-42) aggregates, a hallmark of AD pathology, we used them to investigate cellular mediators of Aβ1-42 toxicity. We observed in neurons differentiated from both hiPS cell lines that Aβ induced toxicity correlated with cell cycle re-entry and was inhibited by pharmacological inhibitors or shRNAs against Cyclin-dependent kinase 2 (Cdk2). As one of the hiPS cell lines has been developed commercially to supply large quantities of differentiated neurons (iCell® Neurons), we screened a chemical library containing several hundred compounds and discovered several small molecules as effective blockers against Aβ1-42 toxicity, including a Cdk2 inhibitor. To our knowledge, this is the first demonstration of an Aβ toxicity screen using hiPS cell-derived neurons. This study provided an excellent example of how hiPS cells can be used for disease modeling and high-throughput compound screening for neurodegenerative diseases.

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The skyrocketing popularity of health monitoring has spurred increasing interest in wearable electrochemical biosensors. Compared with the traditionally rigid and bulky electrochemical biosensors, flexible and stretchable devices render a unique capability to conform to the complex, hierarchically textured surfaces of the human body. With a recognition element (e.g., enzymes, antibodies, nucleic acids, ions) to selectively react with the target analyte, wearable electrochemical biosensors can convert the types and concentrations of chemical changes in the body into electrical signals for easy readout. Initial exploration of wearable electrochemical biosensors integrates electrodes on textile and flexible thin-film substrate materials. A stretchable property is needed for the thin-film device to form an intimate contact with the textured skin surface and to deform with various natural skin motions. Thus, stretchable materials and structures have been exploited to ensure the effective function of a wearable electrochemical biosensor. In this mini-review, we summarize the recent development of flexible and stretchable electrochemical biosensors, including their principles, representative application scenarios (e.g., saliva, tear, sweat, and interstitial fluid), and materials and structures. While great strides have been made in the wearable electrochemical biosensors, challenges still exist, which represents a small fraction of opportunities for the future development of this burgeoning field.