Single-cell encoded gene silencing for high-throughput combinatorial siRNA screening.

The use of combinatorial siRNAs shows great promise for drug discovery, but the identification of safe and effective siRNA combinations remains challenging. Here, we develop a massively multiplexed technology for systematic screening of siRNA-based cocktail therapeutics. We employ composite micro-carriers that are responsive to near infrared light and magnetic field to achieve photoporation-facilitated siRNA transfection to individual cells.

Vertebrates on a Chip: Noninvasive Electrical and Optical Mapping of Whole Brain Activity Associated with Pharmacological Treatments.

Mapping brain activities is necessary for understanding brain physiology and discovering new treatments for neurological disorders. Such efforts have greatly benefited from the advancement in technologies for analyzing neural activity with improving temporal or spatial resolution. Here, we constructed a multielectrode array based brain activity mapping (BAM) system capable of stabilizing and orienting zebrafish larvae for recording electroencephalogram (EEG) like local field potential (LFP) signals and brain-wide calcium dynamics in awake zebrafish.

Self-Healing Electronics for Prognostic Monitoring of Methylated Circulating Tumor DNAs.

Methylated circulating DNAs (ctDNAs) have recently been reported as a promising biomarker for early cancer diagnostics, but limited tools are currently available for continuous and dynamic profiling of ctDNAs and their methylation levels, especially when such assays need to be conducted in point-of-care (POC) scenarios. Here, a self-healing bioelectronic patch (iMethy) is developed that combines transdermal interstitial fluid (ISF) extraction and field effect transistor-based (FET-based) biosensing for dynamic monitoring of methylated ctDNAs as a prognostic approach for cancer risk management. The projection micro-stereolithography-based 3D patterning of an Eutectic Gallium-Indium (EGaIn) circuit with an unprecedented 10 µm resolution enables the construction of self-healing EGaIn microfluidic circuits that remain conductive under 100% strain and self-healing under severe destruction.

Ca2+ Oscillations, Waves, and Networks in Islets From Human Donors With and Without Type 2 Diabetes.

Pancreatic islets are highly interconnected structures that produce pulses of insulin and other hormones, maintaining normal homeostasis of glucose and other nutrients. Normal stimulus-secretion and intercellular coupling are essential to regulated secretory responses, and these hallmarks are known to be altered in diabetes. In the current study, we used calcium imaging of isolated human islets to assess their collective behavior.

3D Upconversion Barcodes for Combinatory Wireless Neuromodulation in Behaving Animals.

Upconversion techniques offer all-optical wireless alternatives to modulate targeted neurons in behaving animals, but most existing upconversion-based optogenetic devices show prefixed emission that is used to excite just one channelrhodopsin at a restricted brain region. Here, a hierarchical upconversion device is reported to enable spatially selective and combinatory optogenetics in behaving rodent animals. The device assumes a multiarrayed optrode format containing engineered upconversion nanoparticles (UCNPs) to deliver dynamic light palettes as a function of excitation wavelength.

Transplantation of Human Pancreatic Endoderm Cells Reverses Diabetes Post Transplantation in a Prevascularized Subcutaneous Site.

Beta-cell replacement therapy is an effective means to restore glucose homeostasis in select humans with autoimmune diabetes. The scarcity of "healthy" human donor pancreata restricts the broader application of this effective curative therapy. "β-Like" cells derived from human embryonic stem cells (hESC), with the capacity to secrete insulin in a glucose-regulated manner, have been developed in vitro, with limitless capacity for expansion.

Impaired "Glycine"-mia in Type 2 Diabetes and Potential Mechanisms Contributing to Glucose Homeostasis.

The onset and/or progression of type 2 diabetes (T2D) can be prevented if intervention is early enough. As such, much effort has been placed on the search for indicators predictive of prediabetes and disease onset or progression. An increasing body of evidence suggests that changes in plasma glycine may be one such biomarker.

A Glycine-Insulin Autocrine Feedback Loop Enhances Insulin Secretion From Human β-Cells and Is Impaired in Type 2 Diabetes.

The secretion of insulin from pancreatic islet β-cells is critical for glucose homeostasis. Disrupted insulin secretion underlies almost all forms of diabetes, including the most common form, type 2 diabetes (T2D). The control of insulin secretion is complex and affected by circulating nutrients, neuronal inputs, and local signaling.

Autocrine activation of P2Y1 receptors couples Ca (2+) influx to Ca (2+) release in human pancreatic beta cells.

Aims/hypothesis: There is evidence that ATP acts as an autocrine signal in beta cells but the receptors and pathways involved are incompletely understood. Here we investigate the receptor subtype(s) and mechanism(s) mediating the effects of ATP on human beta cells.

Methods: We examined the effects of purinergic agonists and antagonists on membrane potential, membrane currents, intracellular Ca(2+) ([Ca(2+)]i) and insulin secretion in human beta cells.