Integrated internal ion-gated organic electrochemical transistors for stand-alone conformable bioelectronics.

Organic electronics can be biocompatible and conformable, enhancing the ability to interface with tissue. However, the limitations of speed and integration have, thus far, necessitated reliance on silicon-based technologies for advanced processing, data transmission and device powering. Here we create a stand-alone, conformable, fully organic bioelectronic device capable of realizing these functions. This device, vertical internal ion-gated organic electrochemical transistor (vIGT), is based on a transistor architecture that incorporates a vertical channel and a miniaturized hydration access conduit to enable megahertz-signal-range operation within densely packed integrated arrays in the absence of crosstalk. These transistors demonstrated long-term stability in physiologic media, and were used to generate high-performance integrated circuits. We leveraged the high-speed and low-voltage operation of vertical internal ion-gated organic electrochemical transistors to develop alternating-current-powered conformable circuitry to acquire and wirelessly communicate signals. The resultant stand-alone device was implanted in freely moving rodents to acquire, process and transmit neurophysiologic brain signals. Such fully organic devices have the potential to expand the utility and accessibility of bioelectronics to a wide range of clinical and societal applications.

Responsive manipulation of neural circuit pathology by fully implantable, front-end multiplexed embedded neuroelectronics.

Responsive neurostimulation is increasingly required to probe neural circuit function and treat neuropsychiatric disorders. We introduce a multiplex-then-amplify (MTA) scheme that, in contrast to current approaches (which necessitate an equal number of amplifiers as number of channels), only requires one amplifier per multiplexer, significantly reducing the number of components and the size of electronics in multichannel acquisition systems. It also enables simultaneous stimulation of arbitrary waveforms on multiple independent channels. We validated the function of MTA by developing a fully implantable, responsive embedded system that merges the ability to acquire individual neural action potentials using conformable conducting polymer-based electrodes with real-time onboard processing, low-latency arbitrary waveform stimulation, and local data storage within a miniaturized physical footprint. We verified established responsive neurostimulation protocols and developed a network intervention to suppress pathological coupling between the hippocampus and cortex during interictal epileptiform discharges. The MTA design enables effective, self-contained, chronic neural network manipulation with translational relevance to the treatment of neuropsychiatric disease.

Complete genome sequence of a novel fusarivirus from Rhizoctonia solani AG-3 PT strain 3P-2-2.

Here, we describe a novel mycovirus, tentatively designated as "Rhizoctonia solani fusarivirus 6" (RsFV6), which was discovered in Rhizoctonia solani AG-3 PT strain 3P-2-2. The virus has a single-stranded positive-sense RNA (+ssRNA) genome of 6141 nucleotides containing two open reading frames (ORFs) and a poly(A) tail. ORF1 encodes a large polypeptide of 1,862 amino acids (aa) with conserved RNA-dependent RNA polymerase (RdRp) and helicase (Hel) domains. ORF2 encodes a putative 167-aa protein of unknown function. BLASTp searches revealed that the ORF1-encoded polypeptide showed the highest sequence similarity (70.67% identity) to that of Rhizoctonia solani fusarivirus 3 (RsFV3), which was isolated from Rhizoctonia solani AG-2-2LP. Multiple sequence alignments and phylogenetic analysis based on RdRp and Hel sequences indicated that RsFV6 could be a novel member of the genus Alphafusarivirus family Fusariviridae.

Study on Fluorescence Recognition of Fe3+, Cr2O72- and p-Nitrophenol by a Cadmium Complex and Related Mechanism.

The effective detection of environmental pollutants is very important to the sustainable development of human health and the environment. A luminescent Cd(II) coordination complex, {[Cd(dbtdb)(1,2,4-H3btc)]·0.5H2O}n (1) (dbtdb = 1-(2,3,5,6-tetramethyl-4-((2-(thiazol-4-yl)-2H-benzo[d]imidazol-3(3aH)-yl)methyl)benzyl)-2,7a-dihydro-2-(thiazol-4-yl)-1H-benzo[d]imidazole, 1,2,4-H3btc = 1,2,4-benzenetricarboxylic acid), was obtained by hydrothermal reactions. Complex 1 has a chain structure decorated with uncoordinated Lewis basic O and S donors and provides good sensing of Fe3+, Cr2O72-, and p-nitrophenol with fluorescence quenching through an energy transfer process. The calculated binding constants were 3.3 × 103 mol-1 for Fe3+, 2.36 × 104 mol-1 for Cr2O72-, and 9.3 × 103 mol-1 for p-nitrophenol, respectively. These results show that 1 is a rare multiresponsive sensory material for efficient detection of Fe3+, Cr2O72-, and p-nitrophenol.

Comparative Study of Docosahexaenoic Acid with Different Molecular Forms for Promoting Apoptosis of the 95D Non-Small-Cell Lung Cancer Cells in a PPARγ-Dependent Manner.

Cancer is a leading cause of death in worldwide. Growing evidence has shown that docosahexaenoic acid (DHA) has ameliorative effects on cancer. However, the effects of DHA-enriched phosphatidylcholine (DHA-PC) and efficacy differences between DHA-PC, DHA-triglyceride (DHA-TG), and DHA- ethyl esters (DHA-EE) on cancer cells had not been studied. In this study, 95D lung cancer cells in vitro were used to determine the effects and underlying mechanisms of DHA with different molecular forms. The results showed that DHA-PC and DHA-TG treatment significantly inhibited the growth of 95D cells by 53.7% and 33.8%, whereas DHA-EE had no significantly effect. Morphological analysis showed that DHA-PC and DHA-TG prompted promoted cell contraction, increased concentration of cell heterochromatin, vacuolization of cytoplasm, and edema of endoplasmic reticulum and mitochondria. TUNEL and AO/EB staining indicated that both DHA-PC and DHA-TG promoted cell apoptosis, in which DHA-PC performed better than DHA-TG. Mechanistically, DHA-PC and DHA-TG treatment up-regulated the PPARγ and RXRα signal, inhibited the expression of NF-κB and Bcl-2, and enhanced the expression of Bax and caspase-3, thereby promoting cell apoptosis. In conclusion, DHA-PC exerted superior effects to DHA-TG and DHA-EE in promoting apoptosis in 95D non-small-cell lung cancer cells. These data provide new evidence for the application of DHA in treatment of cancer.

Molecular characterization of a novel mycovirus isolated from Rhizoctonia solani AG-1 IA strain 9-11.

The complete genome sequence of a double-stranded RNA (dsRNA) virus, Rhizoctonia solani dsRNA virus 11 (RsRV11), isolated from Rhizoctonia solani AG-1 IA strain 9-11 was determined. The RsRV11 genome is 9,555 bp in length and contains three conserved domains: structural maintenance of chromosomes (SMC) superfamily, phosphoribulokinase (PRK), and RNA-dependent RNA polymerase (RdRp). The RsRV11 genome has two non-overlapping open reading frames (ORFs). ORF1 is predicted to encode a 204.12-kDa protein that shares low but significant amino acid sequence similarity with a putative protein encoded by Rhizoctonia solani RNA virus HN008 (RsRV-HN008). ORF2 potentially encodes a 132.41-kDa protein that contains the conserved domain of the RdRp. Phylogenetic analysis indicated that RsRV11 clustered with RsRV-HN008 in a separate clade from other virus families. This implies that RsRV11 and RsRV-HN008 should be included in a new mycovirus taxon close to the family Megabirnaviridae and that RsRV11 is a new mycovirus.

Direct Self-Assembly of MXene on Zn Anodes for Dendrite-Free Aqueous Zinc-Ion Batteries.

Metallic zinc is a promising anode candidate of aqueous zinc-ion batteries owing to its high theoretical capacity and low redox potential. However, Zn anodes usually suffer from dendrite and side reactions, which will degrade their cycle stability and reversibility. Herein, we developed an in situ spontaneously reducing/assembling strategy to assemble a ultrathin and uniform MXene layer on the surface of Zn anodes. The MXene layer endows the Zn anode with a lower Zn nucleation energy barrier and a more uniformly distributed electric field through the favorable charge redistribution effect in comparison with pure Zn. Therefore, MXene-integrated Zn anode exhibits obviously low voltage hysteresis and excellent cycling stability with dendrite-free behaviors, ensuring the high capacity retention and low polarization potential in zinc-ion batteries.

The Potential Role of Synanthropic Rodents and Flies in the Transmission of Enterocytozoon bieneusi on a Dairy Cattle farm in China.

Enterocytozoon bieneusi causes microsporidiosis, a condition with complex epidemiology involving both direct and indirect transmission routes. To assess the potential role of synanthropic rodents and flies in the transmission of this pathogen, a total of 277 cattle fecal samples, 199 synanthropic rodents, and 50 batches of 20 flies were collected from a cattle farm. These samples were screened for the presence of E. bieneusi by PCR and sequencing of the internal transcribed spacer (ITS) region of the rRNA gene. The positive rates of cattle, synanthropic rodents, and flies were 11.9% (33/277), 4.0% (8/199) and 12.0% (6/50), respectively. Nineteen genotypes were identified, including 11 known genotypes (BEB6, I, COS-I, EbpC, D, J, CHS5, CHG1 to CHG3 and CHG14) and eight novel genotypes (named CHC9 to CHC16). The dominant genotype detected in the present study, BEB6, was found in all three categories of hosts. Moreover, human pathogenic genotypes D and EbpC were also observed in both synanthropic rodents and flies. These results demonstrate that synanthropic rodents and flies may act as biological disseminator or mechanical vector in the transmission of microsporidiosis to humans. Efforts should be made to minimize threats from these commensal animals to public health.

Electrophysiological Signature of Pain.

Pain is a complex neural function involving cognition, sensory, emotion, and memory. Imaging studies have shown that multiple brain regions are actively engaged in the processing of pain. However, roles of each brain regions and their contribution to pain are still largely unknown. Recent studies with electrophysiology especially high-density electroencephalogram (EEG) or multichannel recordings techniques have provided more insights into the dynamics of pain signature. The accumulations of the evidence could facilitate our understanding of pain and provide potential methods for objective pain evaluation and treatment of chronic pain.

Caseinophosphopeptides Overcome Calcium Phytate Inhibition on Zinc Bioavailability by Retaining Zinc from Coprecipitation as Zinc/Calcium Phytate Nanocomplexes.

Caseinophosphopeptides have shown great potential to increase zinc bioavailability from phytate-rich diets, but the mechanism of action remains unclear. Here, caseinophosphopeptides from a sodium caseinate hydrolysate dose-dependently retained zinc in solution against calcium phytate coprecipitation under physiologically relevant conditions. The 3 kDa ultrafiltration separation unveiled no added low-molecular-weight chelates of zinc and calcium by caseinophosphopeptides. Tyndall effect, dynamic light scattering measurements, transmission electron microscopy observation, electron diffraction pattern, X-ray diffraction spectrum, and energy-dispersive X-ray analysis demonstrated the caseinophosphopeptides-mediated formation of single-crystal zinc/calcium phytate nanocomplexes (Zn/CaPA-NCs) with a size and ζ-potential of 10-30 nm and -25 mV, respectively. Caseinophosphopeptides-stabilized Zn/CaPA-NCs were found to deliver bioavailable nanoparticulate zinc in mouse jejunal loop ex vivo model and polarized Caco-2 cells, and the treatments with specific inhibitors revealed that intestinal zinc absorption from Zn/CaPA-NCs invoked macropinocytosis, lysosomal release into the cytosol, and transcytosis. Overall, our study proposes a new paradigm for the benefit of caseinophosphopeptides for zinc bioaccessibility and bioavailability in phytate-rich diets.

Glycogen and zinc-enriched ferritin as bioavailable nanoparticulate nutrients released from gastrointestinal digestion of pacific oyster (Crassostrea gigas).

Oyster is a low-carbon animal food enriched with protein, glycogen, and trace minerals. Nano-nutrients are increasingly perceived as an unignorable part of foods. Here, simulated gastrointestinal digestion released a considerable amount of nanoparticulate nutrients from raw and cooked oysters. They were identified as glycogen monomers with size of 20-40 nm and their aggregates, as well as 6 nm-sized bare cores of ferritin containing iron and zinc (4:1, w/w). FITC-labeling and flow cytometry unveiled the efficient uptake of oyster glycogen by polarized Caco-2 cells via macropinocytosis and receptor-mediated endocytosis. Calcein-fluorescence-quenching assay revealed divalent-metal-transporter-1- and macropinocytosis-mediated enterocyte iron absorption from oyster ferritin. Zinquin-fluorescence flow cytometry and ex-vivo mouse ileal loop experiments demonstrated the ready intestinal zinc absorption from oyster ferritin via macropinocytosis, as well as the good resistance of oyster ferritin to phytate's inhibition on zinc absorption. Overall, our results offer a new insight into the digestive and chemical properties of oysters.

Gum Arabic-Derived Hydroxyproline-Rich Peptides Stimulate Intestinal Nonheme Iron Absorption via HIF2α-Dependent Upregulation of Iron Transport Proteins.

The stimulation of host iron absorption is a promising antianemia strategy adjunctive/alternative to iron intervention. Here, gum arabic (GA) containing 3.14 ± 0.56% hydroxyproline-rich protein with repetitive X-(Pro/Hyp)n motifs was found to increase iron reduction, uptake, and transport to upregulate duodenal cytochrome b (Dcytb), divalent metal transporter 1 (DMT1), ferroportin, and hephaestin to inhibit hypoxia-inducible factor (HIF) prolyl hydroxylase (PHD) and to stabilize HIF2α in polarized Caco-2 cell monolayers in a dose-dependent manner, and this was dependent on its protein fraction, rather than the polysaccharide fraction. Three abundant GA-derived hydroxyproline-containing dipeptides of Hyp-Hyp, Pro-Hyp, and Ser-Hyp were detected by liquid chromatography-mass spectrometry in the lysates of polarized Caco-2 cell monolayers at the maximum levels of  0.167 ± 0.021, 0.134 ± 0.017, and 0.089 ± 0.015 µg/mg of protein, respectively, and showed desirable docking affinity energy values of -7.53, - 7.91, and -7.39 kcal/mol, respectively, against human PHD3. GA-derived peptides also acutely increased duodenal HIF2α stability and Dcytb, DMT1, ferroportin, and hephaestin transcription in rats (P < 0.05). Overall, GA-derived hydroxyproline-rich peptides stimulated intestinal iron absorption via PHD inhibition, HIF2α stabilization, and subsequent upregulation of iron transport proteins.

Formation of Anisotropic Conducting Interlayer for High-Resolution Epidermal Electromyography Using Mixed-Conducting Particulate Composite.

Epidermal electrophysiology is a non-invasive method used in research and clinical practices to study the electrical activity of the brain, heart, nerves, and muscles. However, electrode/tissue interlayer materials such as ionically conducting pastes can negatively affect recordings by introducing lateral electrode-to-electrode ionic crosstalk and reducing spatial resolution. To overcome this issue, biocompatible, anisotropic-conducting interlayer composites (ACI) that establish an electrically anisotropic interface with the skin are developed, enabling the application of dense cutaneous sensor arrays. High-density, conformable electrodes are also microfabricated that adhere to the ACI and follow the curvilinear surface of the skin. The results show that ACI significantly enhances the spatial resolution of epidermal electromyography (EMG) recording compared to conductive paste, permitting the acquisition of single muscle action potentials with distinct spatial profiles. The high-density EMG in developing mice, non-human primates, and humans is validated. Overall, high spatial-resolution epidermal electrophysiology enabled by ACI has the potential to advance clinical diagnostics of motor system disorders and enhance data quality for human-computer interface applications.

Closed-loop electrical stimulation to prevent focal epilepsy progression and long-term memory impairment.

Interictal epileptiform discharges (IEDs) are ubiquitously expressed in epileptic networks and disrupt cognitive functions. It is unclear whether addressing IED-induced dysfunction could improve epilepsy outcomes as most therapeutics target seizures. We show in a model of progressive hippocampal epilepsy that IEDs produce pathological oscillatory coupling which is associated with prolonged, hypersynchronous neural spiking in synaptically connected cortex and expands the brain territory capable of generating IEDs. A similar relationship between IED-mediated oscillatory coupling and temporal organization of IEDs across brain regions was identified in human subjects with refractory focal epilepsy. Spatiotemporally targeted closed-loop electrical stimulation triggered on hippocampal IED occurrence eliminated the abnormal cortical activity patterns, preventing spread of the epileptic network and ameliorating long-term spatial memory deficits in rodents. These findings suggest that stimulation-based network interventions that normalize interictal dynamics may be an effective treatment of epilepsy and its comorbidities, with a low barrier to clinical translation. One-Sentence Summary: Targeted closed-loop electrical stimulation prevents spread of the epileptic network and ameliorates long-term spatial memory deficits.

Plant electrophysiology with conformable organic electronics: Deciphering the propagation of Venus flytrap action potentials.

Electrical signals in plants are mediators of long-distance signaling and correlate with plant movements and responses to stress. These signals are studied with single surface electrodes that cannot resolve signal propagation and integration, thus impeding their decoding and link to function. Here, we developed a conformable multielectrode array based on organic electronics for large-scale and high-resolution plant electrophysiology. We performed precise spatiotemporal mapping of the action potential (AP) in Venus flytrap and found that the AP actively propagates through the tissue with constant speed and without strong directionality. We also found that spontaneously generated APs can originate from unstimulated hairs and that they correlate with trap movement. Last, we demonstrate that the Venus flytrap circuitry can be activated by cells other than the sensory hairs. Our work reveals key properties of the AP and establishes the capacity of organic bioelectronics for resolving electrical signaling in plants contributing to the mechanistic understanding of long-distance responses in plants.

E-Suture: Mixed-Conducting Suture for Medical Devices.

Modern implantable bioelectronics demand soft, biocompatible components that make robust, low-impedance connections with the body and circuit elements. Concurrently, such technologies must demonstrate high efficiency, with the ability to interface between the body's ionic and external electronic charge carriers. Here, a mixed-conducting suture, the e-suture, is presented. Composed of silk, the conducting polymer poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS), and insulating jacketing polymers,the resulting e-suture has mixed-conducting properties at the interface with biological tissue as well as effective insulation along its length. The e-suture can be mechanically integrated into electronics, enabling the acquisition of biopotentials such as electrocardiograms, electromyograms, and local field potentials (LFP). Chronic, in vivo acquisition of LFP with e-sutures remains stable for months with robust brain activity patterns. Furthermore, e-sutures can establish electrophoretic-based local drug delivery, potentially offering enhanced anatomical targeting and decreased side effects associated with systemic administration, while maintaining an electrically conducting interface for biopotential monitoring. E-sutures expand on the conventional role of sutures and wires by providing a soft, biocompatible, and mechanically sound structure that additionally has multifunctional capacity for sensing, stimulation, and drug delivery.

Cd(II)/Mn(II)/Co(II)/Ni(II)/Zn(II) Coordination Polymers Built from Dicarboxylic Acid/Tetracarboxylic Acid Ligands: Their Structural Diversity and Fluorescence Properties.

Six Cd(II)/Mn(II)/Co(II)/Ni(II)/Zn(II) coordination complexes are formulated as [Cd2(X2-)2(µ3-O)2/3]n (1), [Mn2(X2-)2(µ3-O)2/3]n (2), {[Co1.5(Y4-)0.5(4,4'-bpy)1.5(OH-)]·2H2O}n (3), {[Ni(X2-)(4,4'-bpy)(H2O)2]·4H2O}n (4), [Zn(m-bdc2-)(bebiyh)]n (5), and [Cd(5-tbia2-)(bebiyh)]n (6) (H2X = 3,3'-(2,3,5,6-tetramethyl-1,4-phenylene) dipropionic acid. H4Y = 2,2'-(2,3,5,6-tetramethyl-1,4-phenylene)bis(methylene) dimalonic acid, bebiyh = 1,6-bis(2-ethyl-1H-benzo[d]imidazol-1-yl)hexane, m-H2bdc = 1,3-benzenedicarboxylic acid, and 5-H2tbia = 5-(tert-butyl)isophthalic acid) were obtained by hydrothermal reactions and structurally characterized. Complexes 1 and 2 have a 6-connected 3D architecture and with several point symbols of (36·46·53). Complex 3 features a 5-connected 3D net structure with a point symbol of (5·69). Complex 4 possesses a 4-connected 2D net with a vertex symbol of (44·62). Complex 5 is a 3-connected 2D network with a point symbol of (63). Complex 6 is a (3,3)-connected 2D network with a point symbol of (63)2. In addition, complexes 1 and 4 present good photoluminescence behaviors. The electronic structures of 1 and 4 were investigated with the density functional theory (DFT) method to understand the photoluminescence behaviors.

Dorsal root ganglion pulsed radiofrequency using bipolar technology in patients with lumbosacral radicular pain duration ≥ 2 years.

Background: Transforaminal epidural steroid injection (TFESI) or dorsal root ganglion pulsed radiofrequency (PRF) are alternative treatments for lumbosacral radicular pain (LSRP). This study aimed to investigate the clinical efficacy of TFESI combined with dorsal root ganglion PRF using bipolar technology to treat LSRP in patients with pain duration ≥ 2 years. Methods: This prospective single-armed cohort study included 20 patients with LSRP duration ≥ 2 years, who underwent treatment of TFESI combined with bipolar PRF. The primary outcomes included numerical rating scale (NRS) and successful treatment rate (pain relief ≥50%). The secondary outcomes included Oswestry Disability Index (ODI), patient satisfaction using the modified MacNab criteria, severe complications, hospital stay and total costs. The final follow-up was 6 months postoperatively. Results: The successful treatment rate and average pain relief at 6 months postoperatively were 80% and 73.0% ± 17.5%, respectively. The successful treatment rates in patients with and without prior intervention history at 6 months postoperatively were 77.8% and 81.8%, respectively. The mean NRS score significantly decreased from 6.5 ± 0.8 to 1.1 ± 0.7 at 2 weeks postoperatively, to 1.3 ± 0.7 at 3 months postoperatively, and to 1.7 ± 1.0 at 6 months postoperatively (all P < 0.001), while the mean ODI score significantly decreased from 43.5 ± 2.5 to 22.5 ± 4.3 at 2 weeks postoperatively, to 20.0 ± 3.5 at 3 months postoperatively, and to 19.5 ± 3.6 at 6 months postoperatively (all P < 0.001). The excellent and good patient satisfaction at 6 months postoperatively was 85%. No severe complications were observed in this cohort. The average hospital stay and total costs were 3.0 ± 0.5 days and 3.36 ± 0.77 thousand dollars, respectively. Conclusion: The treatment of TFESI combined with PRF using bipolar technology might be an alternative option to treat chronic LSRP in patients with pain duration ≥ 2 years after a failure of conservative treatments, with a favorable 6-month efficacy and inexpensive total costs. However, long-term outcomes and superiority of bipolar procedure over monopolar procedure in patients with longer pain duration should be further investigated in future studies.

Deep Brain Stimulation (DBS) with Subthalamic Nucleus (STN) as Target for Pediatric Patients with PKAN.

OBJECTIVE: Dystonia in pantothenate kinase-associated neurodegeneration (PKAN) is progressive despite medication. Deep brain stimulation (DBS) was reported to effectively provide symptom relief. No consensus exists in candidate and target selection for DBS. We aimed to demonstrate effectiveness of subthalamic DBS (STN-DBS) placement in pediatric patients with PKAN. METHODS: We reviewed consecutive series of pediatric patients diagnosed with PKAN and treated with STN-DBS from 2016 to 2019 in our institution. Each case was described in detail. Preoperative and postoperative Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) were assessed to evaluate functional improvement at follow-up. RESULTS: Seven pediatric patients were included. Mean age of initial onset was 0.6 ± 0.5 years and presentation to clinics was 6.6 ± 1.3 years. Mean preoperative BFMDRS was 73.3 ± 3.5. Following STN-DBS, for mean follow-up duration of 13.0 ± 10.7 months, mean BFMDRS was 37.3 ± 12.6, translating to score improvement of 36.0 ± 12.9 (P < 0.001), and percentage improvement of 49.0 ± 18.0%. CONCLUSIONS: This case series demonstrated that STN-DBS is an effective symptom-based treatment for pediatric patients with PKAN.

Ionic communication for implantable bioelectronics.

Implanted bioelectronic devices require data transmission through tissue, but ionic conductivity and inhomogeneity of this medium complicate conventional communication approaches. Here, we introduce ionic communication (IC) that uses ions to effectively propagate megahertz-range signals. We demonstrate that IC operates by generating and sensing electrical potential energy within polarizable media. IC was tuned to transmit across a range of biologically relevant tissue depths. The radius of propagation was controlled to enable multiline parallel communication, and it did not interfere with concurrent use of other bioelectronics. We created a fully implantable IC-based neural interface device that acquired and noninvasively transmitted neurophysiologic data from freely moving rodents over a period of weeks with stability sufficient for isolation of action potentials from individual neurons. IC is a biologically based data communication that establishes long-term, high-fidelity interactions across intact tissue.