Capacitive and Efficient Near-Infrared Stimulation of Neurons via an Ultrathin AgBiS2 Nanocrystal Layer.

Colloidal nanocrystals (NCs) exhibit significant potential for photovoltaic bioelectronic interfaces because of their solution processability, tunable energy levels, and inorganic nature, lending them chemical stability. Silver bismuth sulfide (AgBiS2) NCs, free from toxic heavy-metal elements (e.g., Cd, Hg, and Pb), particularly offer an exceptional absorption coefficient exceeding 105 cm-1 in the near-infrared (NIR), surpassing many of their inorganic counterparts. Here, we integrated an ultrathin (24 nm) AgBiS2 NC layer into a water-stable photovoltaic bioelectronic device architecture that showed a high capacitive photocurrent of 2.3 mA·cm-2 in artificial cerebrospinal fluid (aCSF) and ionic charges over 10 µC·cm-2 at a low NIR intensity of 0.5 mW·mm-2. The device without encapsulation showed a halftime of 12.5 years under passive accelerated aging test and did not show any toxicity on neurons. Furthermore, patch-clamp electrophysiology on primary hippocampal neurons under whole-cell configuration revealed that the device elicited neuron firing at intensity levels more than an order of magnitude below the established ocular safety limits. These findings point to the potential of AgBiS2 NCs for photovoltaic retinal prostheses.

A Retina-Inspired Optoelectronic Synapse Using Quantum Dots for Neuromorphic Photostimulation of Neurons.

Neuromorphic electronics, inspired by the functions of neurons, have the potential to enable biomimetic communication with cells. Such systems require operation in aqueous environments, generation of sufficient levels of ionic currents for neurostimulation, and plasticity. However, their implementation requires a combination of separate devices, such as sensors, organic synaptic transistors, and stimulation electrodes. Here, a compact neuromorphic synapse that combines photodetection, memory, and neurostimulation functionalities all-in-one is presented. The artificial photoreception is facilitated by a photovoltaic device based on cell-interfacing InP/ZnS quantum dots, which induces photo-faradaic charge-transfer mediated plasticity. The device sends excitatory post-synaptic currents exhibiting paired-pulse facilitation and post-tetanic potentiation to the hippocampal neurons via the biohybrid synapse. The electrophysiological recordings indicate modulation of the probability of action potential firing due to biomimetic temporal summation of excitatory post-synaptic currents. The results pave the way for the development of novel bioinspired neuroprosthetics and soft robotics and highlight the potential of quantum dots for achieving versatile neuromorphic functionality in aqueous environments.

A Retina-Inspired Optoelectronic Synapse Using Quantum Dots for Neuromorphic Photostimulation of Neurons.

Neuromorphic electronics, inspired by the functions of neurons, have the potential to enable biomimetic communication with cells. Such systems require operation in aqueous environments, generation of sufficient levels of ionic currents for neurostimulation, and plasticity. However, their implementation requires a combination of separate devices, such as sensors, organic synaptic transistors, and stimulation electrodes. Here, a compact neuromorphic synapse that combines photodetection, memory, and neurostimulation functionalities all-in-one is presented. The artificial photoreception is facilitated by a photovoltaic device based on cell-interfacing InP/ZnS quantum dots, which induces photo-faradaic charge-transfer mediated plasticity. The device sends excitatory post-synaptic currents exhibiting paired-pulse facilitation and post-tetanic potentiation to the hippocampal neurons via the biohybrid synapse. The electrophysiological recordings indicate modulation of the probability of action potential firing due to biomimetic temporal summation of excitatory post-synaptic currents. These results pave the way for the development of novel bioinspired neuroprosthetics and soft robotics, and highlight the potential of quantum dots for achieving versatile neuromorphic functionality in aqueous environments.

MnO2 Nanoflower Integrated Optoelectronic Biointerfaces for Photostimulation of Neurons.

Optoelectronic biointerfaces have gained significant interest for wireless and electrical control of neurons. Three-dimentional (3D) pseudocapacitive nanomaterials with large surface areas and interconnected porous structures have great potential for optoelectronic biointerfaces that can fulfill the requirement of high electrode-electrolyte capacitance to effectively transduce light into stimulating ionic currents. In this study, the integration of 3D manganese dioxide (MnO2 ) nanoflowers into flexible optoelectronic biointerfaces for safe and efficient photostimulation of neurons is demonstrated. MnO2 nanoflowers are grown via chemical bath deposition on the return electrode, which has a MnO2 seed layer deposited via cyclic voltammetry. They facilitate a high interfacial capacitance (larger than 10 mF cm-2 ) and photogenerated charge density (over 20 µC cm-2 ) under low light intensity (1 mW mm-2 ). MnO2 nanoflowers induce safe capacitive currents with reversible Faradaic reactions and do not cause any toxicity on hippocampal neurons in vitro, making them a promising material for biointerfacing with electrogenic cells. Patch-clamp electrophysiology is recorded in the whole-cell configuration of hippocampal neurons, and the optoelectronic biointerfaces trigger repetitive and rapid firing of action potentials in response to light pulse trains. This study points out the potential of electrochemically-deposited 3D pseudocapacitive nanomaterials as a robust building block for optoelectronic control of neurons.

Electrical Stimulation of Neurons with Quantum Dots via Near-Infrared Light.

Photovoltaic biointerfaces offer wireless and battery-free bioelectronic medicine via photomodulation of neurons. Near-infrared (NIR) light enables communication with neurons inside the deep tissue and application of high photon flux within the ocular safety limit of light exposure. For that, nonsilicon biointerfaces are highly demanded for thin and flexible operation. Here, we devised a flexible quantum dot (QD)-based photovoltaic biointerface that stimulates cells within the spectral tissue transparency window by using NIR light (λ = 780 nm). Integration of an ultrathin QD layer of 25 nm into a multilayered photovoltaic architecture enables transduction of NIR light to safe capacitive ionic currents that leads to reproducible action potentials on primary hippocampal neurons with high success rates. The biointerfaces exhibit low in vitro toxicity and robust photoelectrical performance under different stability tests. Our findings show that colloidal quantum dots can be used in wireless bioelectronic medicine for brain, heart, and retina.

Tissue-Like Optoelectronic Neural Interface Enabled by PEDOT:PSS Hydrogel for Cardiac and Neural Stimulation.

Optoelectronic biointerfaces have made a significant impact on modern science and technology from understanding the mechanisms of the neurotransmission to the recovery of the vision for blinds. They are based on the cell interfaces made of organic or inorganic materials such as silicon, graphene, oxides, quantum dots, and π-conjugated polymers, which are dry and stiff unlike a cell/tissue environment. On the other side, wet and soft hydrogels have recently been started to attract significant attention for bioelectronics because of its high-level tissue-matching biomechanics and biocompatibility. However, it is challenging to obtain optimal opto-bioelectronic devices by using hydrogels requiring device, heterojunction, and hydrogel engineering. Here, an optoelectronic biointerface integrated with a poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate), PEDOT:PSS, hydrogel that simultaneously achieves efficient, flexible, stable, biocompatible, and safe photostimulation of cells is demonstrated. Besides their interfacial tissue-like biomechanics, ≈34 kPa, and high-level biocompatibility, hydrogel-integration facilitates increase in charge injection amounts sevenfolds with an improved responsivity of 156 mA W-1 , stability under mechanical bending , and functional lifetime over three years. Finally, these devices enable stimulation of individual hippocampal neurons and photocontrol of beating frequency of cardiac myocytes via safe charge-balanced capacitive currents. Therefore, hydrogel-enabled optoelectronic biointerfaces hold great promise for next-generation wireless neural and cardiac implants.

Protein Kinase C Isozymes and Autophagy during Neurodegenerative Disease Progression.

Protein kinase C (PKC) isozymes are members of the Serine/Threonine kinase family regulating cellular events following activation of membrane bound phospholipids. The breakdown of the downstream signaling pathways of PKC relates to several disease pathogeneses particularly neurodegeneration. PKC isozymes play a critical role in cell death and survival mechanisms, as well as autophagy. Numerous studies have reported that neurodegenerative disease formation is caused by failure of the autophagy mechanism. This review outlines PKC signaling in autophagy and neurodegenerative disease development and introduces some polyphenols as effectors of PKC isozymes for disease therapy.

Molecular Pathogenesis of Nonalcoholic Steatohepatitis- (NASH-) Related Hepatocellular Carcinoma.

The proportion of obese or diabetic population has been anticipated to increase in the upcoming decades, which rises the prevalence of nonalcoholic fatty liver disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH). Recent evidence indicates that NASH is the main cause of chronic liver diseases and it is an important risk factor for development of hepatocellular carcinoma (HCC). Although the literature addressing NASH-HCC is growing rapidly, limited data is available about the etiology of NASH-related HCC. Experimental studies on the molecular mechanism of HCC development in NASH reveal that the carcinogenesis is relevant to complex changes in signaling pathways that mediate cell proliferation and energy metabolism. Genetic or epigenetic modifications and alterations in metabolic, immunologic, and endocrine pathways have been shown to be closely related to inflammation, liver injury, and fibrosis in NASH along with its subsequent progression to HCC. In this review, we provide an overview on the current knowledge of NASH-related HCC development and emphasize molecular signaling pathways regarding their mechanism of action in NASH-derived HCC.