Stomach region stimulated determines effects on duodenal motility in rats.

Gastric electrical stimulation (GES) is used clinically to promote proximal GI emptying and motility. In acute experiments, we measured duodenal motor responses elicited by GES applied at 141 randomly chosen electrode sites on the stomach serosal surface. Overnight-fasted (H2O available) anesthetized male rats (n = 81) received intermittent biphasic GES for 5 min (20-s-on/40-s-off cycles; I = 0.3 mA; pw = 0.2 ms; 10 Hz). A strain gauge on the serosal surface of the proximal duodenum of each animal was used to evaluate baseline motor activity and the effect of GES. Using ratios of time blocks compared with a 15-min prestimulation baseline, we evaluated the effects of the 5-min stimulation on concurrent activity, on the 10 min immediately after the stimulation, and on the 15-min period beginning with the onset of stimulation. We mapped the magnitude of the duodenal response (three different motility indices) elicited from the 141 stomach sites. Post hoc electrode site maps associated with duodenal responses suggested three zones similar to the classic regions of forestomach, corpus, and antrum. Maximal excitatory duodenal motor responses were elicited from forestomach sites, whereas inhibitory responses occurred with stimulation of the corpus. Moderate excitatory duodenal responses occurred with stimulation of the antrum. Complex, weak inhibitory/excitatory responses were produced by stimulation at boundaries between stomach regions. Patterns of GES efficacies coincided with distributions of previously mapped vagal afferents, suggesting that excitation of the duodenum is strongest when GES electrodes are situated over stomach concentrations of vagal intramuscular arrays, putative stretch receptors in the muscle wall.

Wafer-Scale Growth of Single-Crystal 2D Semiconductor on Perovskite Oxides for High-Performance Transistors.

Emerging two-dimensional (2D) semiconducting materials serve as promising alternatives for next-generation digital electronics and optoelectronics. However, large-scale 2D semiconductor films synthesized so far are typically polycrystalline with defective grain boundaries that could degrade their performance. Here, for the first time, wafer-size growth of a single-crystal Bi2O2Se film, which is a novel air-stable 2D semiconductor with high mobility, was achieved on insulating perovskite oxide substrates [SrTiO3, LaAlO3, (La, Sr)(Al, Ta)O3]. The layered Bi2O2Se epilayer exhibits perfect lattice matching and strong interaction with perovskite oxide substrates, which enable unidirectional alignment and seamless mergence of multiple seeds into single-crystal continuous films free of detrimental grain boundaries. The single-crystal Bi2O2Se thin films show excellent spatial homogeneity over the entire wafer and allow for the batch fabrication of high-performance field-effect devices with high mobilities of ∼150 cm2 V-1 s-1 at room temperature, excellent switching behavior with large on/off ratio of >105, and high drive current of ∼45 µA µm-1 at a channel length of ∼5 µm. Our work makes a step toward the practical applications of high-mobility semiconducting 2D layered materials and provides an alternative platform of oxide heterostructure to investigate novel physical phenomena.

Controlled Synthesis of High-Mobility Atomically Thin Bismuth Oxyselenide Crystals.

Non-neutral layered crystals, another group of two-dimensional (2D) materials that lack a well-defined van der Waals (vdWs) gap, are those that form strong chemical bonds in-plane but display weak out-of-plane electrostatic interactions, exhibiting intriguing properties for the bulk counterpart. However, investigation of the properties of their atomically thin counterpart are very rare presumably due to the absence of efficient ways to achieve large-area high-quality 2D crystals. Here, high-mobility atomically thin Bi2O2Se, a typical non-neutral layered crystal without a standard vdWs gap, was synthesized via a facial chemical vapor deposition (CVD) method, showing excellent controllability for thickness, domain size, nucleation site, and crystal-phase evolution. Atomically thin, large single crystals of Bi2O2Se with lateral size up to ∼200 µm and thickness down to a bilayer were obtained. Moreover, optical and electrical properties of the CVD-grown 2D Bi2O2Se crystals were investigated, displaying a size-tunable band gap upon thinning and an ultrahigh Hall mobility of >20000 cm2 V-1 s-1 at 2 K. Our results on the high-mobility 2D Bi2O2Se semiconductor may activate the synthesis and related fundamental research of other non-neutral 2D materials.

Vertical Graphene Growth on SiO Microparticles for Stable Lithium Ion Battery Anodes.

Silicon-based materials are considered as strong candidates to next-generation lithium ion battery anodes because of their ultrahigh specific capacities. However, the pulverization and delamination of electrochemical active materials originated from the huge volume expansion (>300%) of silicon during the lithiation process results in rapid capacity fade, especially in high mass loading electrodes. Here we demonstrate that direct chemical vapor deposition (CVD) growth of vertical graphene nanosheets on commercial SiO microparticles can provide a stable conducting network via interconnected vertical graphene encapsulation during lithiation, thus remarkably improving the cycling stability in high mass loading SiO anodes. The vertical graphene encapsulated SiO (d-SiO@vG) anode exhibits a high capacity of 1600 mA h/g and a retention up to 93% after 100 cycles at a high areal mass loading of 1.5 mg/cm2. Furthermore, 5 wt % d-SiO@vG as additives increased the energy density of traditional graphite/NCA 18650 cell by ∼15%. We believe that the results strongly imply the important role of CVD-grown vertical graphene encapsulation in promoting the commercial application of silicon-based anodes.

Tuning Chemical Potential Difference across Alternately Doped Graphene p-n Junctions for High-Efficiency Photodetection.

Being atomically thin, graphene-based p-n junctions hold great promise for applications in ultrasmall high-efficiency photodetectors. It is well-known that the efficiency of such photodetectors can be improved by optimizing the chemical potential difference of the graphene p-n junction. However, to date, such tuning has been limited to a few hundred millielectronvolts. To improve this critical parameter, here we report that using a temperature-controlled chemical vapor deposition process, we successfully achieved modulation-doped growth of an alternately nitrogen- and boron-doped graphene p-n junction with a tunable chemical potential difference up to 1 eV. Furthermore, such p-n junction structure can be prepared on a large scale with stable, uniform, and substitutional doping and exhibits a single-crystalline nature. This work provides a feasible method for synthesizing low-cost, large-scale, high efficiency graphene p-n junctions, thus facilitating their applications in optoelectronic and energy conversion devices.

Two-Dimensional (C4H9NH3)2PbBr4 Perovskite Crystals for High-Performance Photodetector.

Two-dimensional (2D) layered hybrid perovskites of (RNH3)2PbX4 (R is an alkyl and X is a halide) have been recently synthesized and exhibited rich optical properties including fluorescence and exciton effects. However, few studies on transport and optoelectronic measurements of individual 2D perovskite crystals have been reported, presumably owing to the instability issue during electronic device fabrications. Here we report the first photodetector based on individual 2D (C4H9NH3)2PbBr4 perovskite crystals, built with the protection and top contact of graphene film. Both a high responsivity (∼2100 A/W) and extremely low dark current (∼10-10 A) are achieved with a design of interdigital graphene electrodes. Our study paves the way to build high-performance optoelectronic devices based on the emerging 2D single-crystal perovskite materials.

Ischemic stroke injury is mediated by aberrant Cdk5.

Ischemic stroke is one of the leading causes of morbidity and mortality. Treatment options are limited and only a minority of patients receive acute interventions. Understanding the mechanisms that mediate neuronal injury and death may identify targets for neuroprotective treatments. Here we show that the aberrant activity of the protein kinase Cdk5 is a principal cause of neuronal death in rodents during stroke. Ischemia induced either by embolic middle cerebral artery occlusion (MCAO) in vivo or by oxygen and glucose deprivation in brain slices caused calpain-dependent conversion of the Cdk5-activating cofactor p35 to p25. Inhibition of aberrant Cdk5 during ischemia protected dopamine neurotransmission, maintained field potentials, and blocked excitotoxicity. Furthermore, pharmacological inhibition or conditional knock-out (CKO) of Cdk5 prevented neuronal death in response to ischemia. Moreover, Cdk5 CKO dramatically reduced infarctions following MCAO. Thus, targeting aberrant Cdk5 activity may serve as an effective treatment for stroke.

Bryostatin improves survival and reduces ischemic brain injury in aged rats after acute ischemic stroke.

BACKGROUND AND PURPOSE: Bryostatin, a potent protein kinase C (PKC) activator, has demonstrated therapeutic efficacy in preclinical models of associative memory, Alzheimer disease, global ischemia, and traumatic brain injury. In this study, we tested the hypothesis that administration of bryostatin provides a therapeutic benefit in reducing brain injury and improving stroke outcome using a clinically relevant model of cerebral ischemia with tissue plasminogen activator reperfusion in aged rats. METHODS: Acute cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery (MCAO) in 18- to 20-month-old female Sprague-Dawley rats using an autologous blood clot with tissue plasminogen activator-mediated reperfusion. Bryostatin was administered at 6 hours post-MCAO, then at 3, 6, 9, 12, 15, and 18 days after MCAO. Functional assessment was conducted at 2, 7, 14, and 21 days after MCAO. Lesion volume and hemispheric swelling/atrophy were performed at 2, 7, and 21 days post-MCAO. Histological assessment of PKC isozymes was performed at 24 hours post-MCAO. RESULTS: Bryostatin-treated rats showed improved survival post-MCAO, especially during the first 4 days. Repeated administration of bryostatin post-MCAO resulted in reduced infarct volume, hemispheric swelling/atrophy, and improved neurological function at 21 days post-MCAO. Changes in αPKC expression and εPKC expression in neurons were noted in bryostatin-treated rats at 24 hours post-MCAO. CONCLUSIONS: Repeated bryostatin administration post-MCAO protected the brain from severe neurological injury post-MCAO. Bryostatin treatment improved survival rate, reduced lesion volume, salvaged tissue in infarcted hemisphere by reducing necrosis and peri-infarct astrogliosis, and improved functional outcome after MCAO.

Robust but delayed thalamocortical activation of dendritic-targeting inhibitory interneurons.

GABA-releasing cortical interneurons are crucial for the neural transformations underlying sensory perception, providing "feedforward" inhibition that constrains the temporal window for synaptic integration. To mediate feedforward inhibition, inhibitory interneurons need to fire in response to ascending thalamocortical inputs, and most previous studies concluded that ascending inputs activate mainly or solely proximally targeting, parvalbumin-containing "fast-spiking" interneurons. However, when thalamocortical axons fire at frequencies that are likely to occur during natural exploratory behavior, activation of fast-spiking interneurons is rapidly and strongly depressed, implying the paradoxical conclusion that feedforward inhibition is absent when it is most needed. To address this issue, we took advantage of lines of transgenic mice in which either parvalbumin- or somatostatin-containing interneurons express GFP and recorded the responses of interneurons from both subtypes to thalamocortical stimulation in vitro. We report that during thalamocortical activation at behaviorally expected frequencies, fast-spiking interneurons were indeed activated only transiently because of rapid depression of their thalamocortical inputs, but a subset of layer 5 somatostatin-containing interneurons were robustly and persistently activated after a delay, due to the facilitation and temporal summation of their thalamocortical excitatory postsynaptic potentials. Somatostatin-containing interneurons are considered distally targeting. Thus, they are likely to provide delayed dendritic inhibition during exploratory behavior, contributing to the maintenance of a balance between cortical excitation and inhibition while leaving a wide temporal window open for synaptic integration and plasticity in distal dendrites.

Author Correction: Ultrafast and highly sensitive infrared photodetectors based on two-dimensional oxyselenide crystals.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Transfer-Medium-Free Nanofiber-Reinforced Graphene Film and Applications in Wearable Transparent Pressure Sensors.

Graphene exhibits properties of atomic thickness, high transparency, and high carrier mobility, which is highly desirable for a flexible transparent conductive material. However, the electronic properties of large-area chemical vapor deposition grown graphene film suffer from insulated polymer contaminations introduced by the transfer process and the easily cracked nature. Here, we report a preparation method of a transfer-medium-free large-area nanofiber-reinforced graphene (a-PAN/G) film simply by annealing the electrostatically spun polyacrylonitrile (PAN) nanofibers on the graphene film. The film could be free-standing on water and suspended in air with high transparency and enhanced electrical and mechanical properties compared to that of a monolayer graphene film. The flexible transparent a-PAN/G films were demonstrated as active materials for sensitive pressure sensors. The obtained pressure sensors demonstrate high sensitivity (44.5 kPa-1 within 1.2 kPa), low operating voltage (0.01-0.5 V), and excellent stability for 5500 loading-unloading cycles, revealing promising potential applications in wearable electronics.

Ultrafast and highly sensitive infrared photodetectors based on two-dimensional oxyselenide crystals.

Infrared light detection and sensing is deeply embedded in modern technology and human society and its development has always been benefitting from the discovery of various photoelectric materials. The rise of two-dimensional materials, thanks to their distinct electronic structures, extreme dimensional confinement and strong light-matter interactions, provides a material platform for next-generation infrared photodetection. Ideal infrared detectors should have fast respond, high sensitivity and air-stability, which are rare to meet at the same time in one two-dimensional material. Herein we demonstrate an infrared photodetector based on two-dimensional Bi2O2Se crystal, whose main characteristics are outstanding in the whole two-dimensional family: high sensitivity of 65 AW-1 at 1200 nm and ultrafast photoresponse of ~1 ps at room temperature, implying an intrinsic material-limited bandwidth up to 500 GHz. Such great performance is attributed to the suitable electronic bandgap and high carrier mobility of two-dimensional oxyselenide.

Low-Temperature Heteroepitaxy of 2D PbI2 /Graphene for Large-Area Flexible Photodetectors.

Heterostructures based on graphene and other 2D atomic crystals exhibit fascinating properties and intriguing potential in flexible optoelectronics, where graphene films function as transparent electrodes and other building blocks are used as photoactive materials. However, large-scale production of such heterostructures with superior performance is still in early stages. Herein, for the first time, the preparation of a submeter-sized, vertically stacked heterojunction of lead iodide (PbI2 )/graphene on a flexible polyethylene terephthalate (PET) film by vapor deposition of PbI2 on graphene/PET substrate at a temperature lower than 200 °C is demonstrated. This film is subsequently used to fabricate bendable graphene/PbI2 /graphene sandwiched photodetectors, which exhibit high responsivity (45 A W-1 cm-2 ), fast response (35 µs rise, 20 µs decay), and high-resolution imaging capability (1 µm). This study may pave a facile pathway for scalable production of high-performance flexible devices.

Chemical Patterning of High-Mobility Semiconducting 2D Bi2 O2 Se Crystals for Integrated Optoelectronic Devices.

Patterning of high-mobility 2D semiconducting materials with unique layered structures and superb electronic properties offers great potential for batch fabrication and integration of next-generation electronic and optoelectronic devices. Here, a facile approach is used to achieve accurate patterning of 2D high-mobility semiconducting Bi2 O2 Se crystals using dilute H2 O2 and protonic mixture acid as efficient etchants. The 2D Bi2 O2 Se crystal after chemical etching maintains a high Hall mobility of over 200 cm2 V-1 s-1 at room temperature. Centimeter-scale well-ordered arrays of 2D Bi2 O2 Se with tailorable configurations are readily obtained. Furthermore, integrated photodetectors based on 2D Bi2 O2 Se arrays are fabricated, exhibiting excellent air stability and high photoresponsivity of ≈2000 A W-1 at 532 nm. These results are one step towards the practical application of ultrathin 2D integrated digital and optoelectronic circuits.

Clean Transfer of Large Graphene Single Crystals for High-Intactness Suspended Membranes and Liquid Cells.

The atomically thin 2D nature of suspended graphene membranes holds promising in numerous technological applications. In particular, the outstanding transparency to electron beam endows graphene membranes great potential as a candidate for specimen support of transmission electron microscopy (TEM). However, major hurdles remain to be addressed to acquire an ultraclean, high-intactness, and defect-free suspended graphene membrane. Here, a polymer-free clean transfer of sub-centimeter-sized graphene single crystals onto TEM grids to fabricate large-area and high-quality suspended graphene membranes has been achieved. Through the control of interfacial force during the transfer, the intactness of large-area graphene membranes can be as high as 95%, prominently larger than reported values in previous works. Graphene liquid cells are readily prepared by π-π stacking two clean single-crystal graphene TEM grids, in which atomic-scale resolution imaging and temporal evolution of colloid Au nanoparticles are recorded. This facile and scalable production of clean and high-quality suspended graphene membrane is promising toward their wide applications for electron and optical microscopy.

Nonlocal Response in Infrared Detector with Semiconducting Carbon Nanotubes and Graphdiyne.

Semiconducting single-walled carbon nanotubes (s-SWNTs) are regarded as an important candidate for infrared (IR) optical detection due to their excellent intrinsic properties. However, the strong binding energy of excitons in s-SWNTs seriously impedes the development of s-SWNTs IR photodetector. This Communication reports an IR photodetector with highly pure s-SWNTs and γ-graphdiyne. The heterojunctions between the two materials can efficiently separate the photogenerated excitons. In comparison to device fabricated only with s-SWNTs, this IR detector shows a uniform response in the whole channel of the device. The response time is demonstrated to be below 1 ms. The optimal responsivity and detectivity approximately reach 0.4 mA W-1 and 5 × 106 cmHz1/2 W-1, respectively.

Selectively enhanced photocurrent generation in twisted bilayer graphene with van Hove singularity.

Graphene with ultra-high carrier mobility and ultra-short photoresponse time has shown remarkable potential in ultrafast photodetection. However, the broad and weak optical absorption (∼ 2.3%) of monolayer graphene hinders its practical application in photodetectors with high responsivity and selectivity. Here we demonstrate that twisted bilayer graphene, a stack of two graphene monolayers with an interlayer twist angle, exhibits a strong light-matter interaction and selectively enhanced photocurrent generation. Such enhancement is attributed to the emergence of unique twist-angle-dependent van Hove singularities, which are directly revealed by spatially resolved angle-resolved photoemission spectroscopy. When the energy interval between the van Hove singularities of the conduction and valance bands matches the energy of incident photons, the photocurrent generated can be significantly enhanced (up to ∼ 80 times with the integration of plasmonic structures in our devices). These results provide valuable insight for designing graphene photodetectors with enhanced sensitivity for variable wavelength.

Building Large-Domain Twisted Bilayer Graphene with van Hove Singularity.

Twisted bilayer graphene (tBLG) with van Hove Singularity (VHS) has exhibited novel twist-angle-dependent chemical and physical phenomena. However, scalable production of high-quality tBLG is still in its infancy, especially lacking the angle controlled preparation methods. Here, we report a facile approach to prepare tBLG with large domain sizes (>100 µm) and controlled twist angles by a clean layer-by-layer transfer of two constituent graphene monolayers. The whole process without interfacial polymer contamination in two monolayers guarantees the interlayer interaction of the π-bond electrons, which gives rise to the existence of minigaps in electronic structures and the consequent formation of VHSs in density of state. Such perturbation on band structure was directly observed by angle-resolved photoemission spectroscopy with submicrometer spatial resolution (micro-ARPES). The VHSs lead to a strong light-matter interaction and thus introduce ∼20-fold enhanced intensity of Raman G-band, which is a characteristic of high-quality tBLG. The as-prepared tBLG with strong light-matter interaction was further fabricated into high-performance photodetectors with selectively enhanced photocurrent generation (up to ∼6 times compared with monolayer in our device).

The role for infarct volume as a surrogate measure of functional outcome following ischemic stroke.

The failed translation of proposed therapeutic agents for ischemic stroke from preclinical to clinical studies has led to increased scrutiny of preclinical studies, namely the model and outcome measures utilized. Preclinical studies routinely use infarct volume as an experimental endpoint or measure in studies employing young-adult, healthy male animals despite the fact that clinically, ischemic stroke is a disease of the elderly and improvements in functional outcome from pre- to post-intervention remains the most widely utilized assessment. The validity of infarct volume as a surrogate measure for functional outcome remains unclear in clinical studies as well as preclinical studies, particularly those utilizing a more clinically relevant aged thromboembolic model. In this work, we will address the relationship between acute and chronic functional outcome and infarct volume using a variety of functional assessments ranging from more simplistic, subjective measurements such as the modified Neurologic Severity Score (mNSS), to more complex, objective measurements such as grip strength and inclined plane.

Bryostatin-1 Restores Blood Brain Barrier Integrity following Blast-Induced Traumatic Brain Injury.

Recent wars in Iraq and Afghanistan have accounted for an estimated 270,000 blast exposures among military personnel. Blast traumatic brain injury (TBI) is the 'signature injury' of modern warfare. Blood brain barrier (BBB) disruption following blast TBI can lead to long-term and diffuse neuroinflammation. In this study, we investigate for the first time the role of bryostatin-1, a specific protein kinase C (PKC) modulator, in ameliorating BBB breakdown. Thirty seven Sprague-Dawley rats were used for this study. We utilized a clinically relevant and validated blast model to expose animals to moderate blast exposure. Groups included: control, single blast exposure, and single blast exposure + bryostatin-1. Bryostatin-1 was administered i.p. 2.5 mg/kg after blast exposure. Evan's blue, immunohistochemistry, and western blot analysis were performed to assess injury. Evan's blue binds to albumin and is a marker for BBB disruption. The single blast exposure caused an increase in permeability compared to control (t = 4.808, p < 0.05), and a reduction back toward control levels when bryostatin-1 was administered (t = 5.113, p < 0.01). Three important PKC isozymes, PKCα, PKCδ, and PKCε, were co-localized primarily with endothelial cells but not astrocytes. Bryostatin-1 administration reduced toxic PKCα levels back toward control levels (t = 4.559, p < 0.01) and increased the neuroprotective isozyme PKCε (t = 6.102, p < 0.01). Bryostatin-1 caused a significant increase in the tight junction proteins VE-cadherin, ZO-1, and occludin through modulation of PKC activity. Bryostatin-1 ultimately decreased BBB breakdown potentially due to modulation of PKC isozymes. Future work will examine the role of bryostatin-1 in preventing chronic neurodegeneration following repetitive neurotrauma.