Low p-SYN1 (Ser-553) Expression Leads to Abnormal Neurotransmitter Release of GABA Induced by Up-Regulated Cdk5 after Microwave Exposure: Insights on Protection and Treatment of Microwave-Induced Cognitive Dysfunction.

With the wide application of microwave technology, concerns about its health impact have arisen. The signal transmission mode of the central nervous system and neurons make it particularly sensitive to electromagnetic exposure. It has been reported that abnormal release of amino acid neurotransmitters is mediated by alteration of p-SYN1 after microwave exposure, which results in cognitive dysfunction. As the phosphorylation of SYN1 is regulated by different kinases, in this study we explored the regulatory mechanisms of SYN1 fluctuations following microwave exposure and its subsequent effect on GABA release, aiming to provide clues on the mechanism of cognitive impairment caused by microwave exposure. In vivo studies with Timm and H&E staining were adopted and the results showed abnormality in synapse formation and neuronal structure, explaining the previously-described deficiency in cognitive ability caused by microwave exposure. The observed alterations in SYN1 level, combined with the results of earlier studies, indicate that SYN1 and its phosphorylation status (ser-553 and ser62/67) may play a role in the abnormal release of neurotransmitters. Thus, the role of Cdk5, the upstream kinase regulating the formation of p-SYN1 (ser-553), as well as that of MEK, the regulator of p-SYN1 (ser-62/67), were investigated both in vivo and in vitro. The results showed that Cdk5 was a negative regulator of p-SYN1 (ser-553) and that its up-regulation caused a decrease in GABA release by reducing p-SYN1 (ser-553). While further exploration still needed to elaborate the role of p-SYN1 (ser-62/67) for neurotransmitter release, MEK inhibition had was no impact on p-Erk or p-SYN1 (ser-62/67) after microwave exposure. In conclusion, the decrease of p-SYN1 (ser-553) may result in abnormalities in vesicular anchoring and GABA release, which is caused by increased Cdk5 regulated through Calpain-p25 pathway after 30 mW/cm2 microwave exposure. This study provided a potential new strategy for the prevention and treatment of microwave-induced cognitive dysfunction.

Large-Scale and Flexible Optical Synapses for Neuromorphic Computing and Integrated Visible Information Sensing Memory Processing.

Optoelectronic synapses integrating synaptic and optical-sensing functions exhibit large advantages in neuromorphic computing for visual information processing and complex learning, recognition, and memory in an energy-efficient way. However, electric stimulation is still essential for existing optoelectronic synapses to realize bidirectional weight-updating, restricting the processing speed, bandwidth, and integration density of the devices. Herein, a two-terminal optical synapse based on a wafer-scale pyrenyl graphdiyne/graphene/PbS quantum dot heterostructure is proposed that can emulate both the excitatory and inhibitory synaptic behaviors in an optical pathway. The simple device architecture and low-dimensional features of the heterostructure endow the optical synapse with robust flexibility for wearable electronics. This optical synapse features a linear and symmetric conductance-update trajectory with numerous conductance states and low noise, which facilitates the demonstration of accurate and effective pattern recognition with a strong fault-tolerant capability even at bending states. A series of logic functions and associative learning capabilities have been demonstrated by the optical synapses in optical pathways, significantly enhancing the information processing capability for neuromorphic computing. Moreover, an integrated visible information sensing memory processing system based on the optical synapse array is constructed to perform real-time detection, in situ image memorization, and distinction tasks. This work is an important step toward the development of optogenetics-inspired neuromorphic computing and adaptive parallel processing networks for wearable electronics.

Laser Writable Multifunctional van der Waals Heterostructures.

Achieving multifunctional van der Waals nanoelectronic devices on one structure is essential for the integration of 2D materials; however, it involves complex architectural designs and manufacturing processes. Herein, a facile, fast, and versatile laser direct write micro/nanoprocessing to fabricate diode, NPN (PNP) bipolar junction transistor (BJT) simultaneously based on a pre-fabricated black phosphorus/molybdenum disulfide heterostructure is demonstrated. The PN junctions exhibit good diode rectification behavior. Due to different carrier concentrations of BP and MoS2 , the NPN BJT, with a narrower base width, renders better performance than the PNP BJT. Furthermore, the current gain can be modulated efficiently through laser writing tunable base width WB , which is consistent with the theoretical results. The maximum gain for NPN and PNP is found to be ≈41 (@WB ≈600 nm) and ≈12 (@WB ≈600 nm), respectively. In addition, this laser write processing technique also can be utilized to realize multifunctional WSe2 /MoS2 heterostructure device. The current work demonstrates a novel, cost-effective, and universal method to fabricate multifunctional nanoelectronic devices. The proposed approach exhibits promise for large-scale integrated circuits based on 2D heterostructures.

Dose-dependent Cardiac Dysfunction and Structural Damage in Rats after Shortwave Radiation.

OBJECTIVE: To detect the effects of shortwave radiation on dose-dependent cardiac structure and function in rats after radiation and to elucidate the mechanism of shortwave radiation induced cardiac injury to identify sensitive indicators and prophylactic treatment. METHODS: One hundred Wistar rats were either exposed to 27 MHz continuous shortwave at a power density of 5, 10, and 30 mW/cm 2 for 6 min or undergone sham exposure for the control (the rats had to be placed in the exposure system with the same schedules as the exposed animals, but with an inactive antenna). The Ca 2+, glutamic oxaloacetic transaminase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) content in the peripheral serum of the rats were detected by an automatic blood biochemical analyser. The electrocardiogram (ECG) of standard lead II was recorded by a multi-channel physiological recording and analysis system. The cardiac structure of rats was observed by light and electron microscopy. RESULTS: The results showed that the 5, 10, and 30 mW/cm 2 shortwave radiation caused a significant increased in the levels of Ca 2+, AST, CK, and LDH in the peripheral serum of rats. The cardiac structure was damaged by radiation and showed a disordered arrangement of myocardial fibres, the cavitation and swelling of myocardial mitochondria. These injuries were most significant 7 d after radiation and were not restored until 28 d after radiation. CONCLUSION: Shortwave radiation of 5, 10, and 30 mW/cm 2 can damage rat cardiac function, including damage to the tissue structure and ultrastructure, especially at the level of the myocardial fibres and mitochondria. Shortwave radiation at 5, 10, and 30 mW/cm 2 induced damage to rat heart function and structure with a dose-effect relationship, i.e., the greater the radiation dose was, the more significant the damage was.

Synthesis of Wafer-Scale Monolayer Pyrenyl Graphdiyne on Ultrathin Hexagonal Boron Nitride for Multibit Optoelectronic Memory.

Graphdiyne is a new two-dimensional carbon allotrope with many attractive properties and has been widely used in various applications. However, the synthesis of large-area, high-quality, and ultrathin (especially monolayer) graphdiyne and its analogues remains a challenge, hindering its application in optoelectronic devices. Here, a wafer-scale monolayer pyrenyl graphdiyne (Pyr-GDY) film is obtained on hexagonal boron nitride (hBN) via a van der Waals epitaxial strategy, and top-floating-gated multibit nonvolatile optoelectronic memory based on Pyr-GDY/hBN/graphene is constructed, using Pyr-GDY as a photoresponsive top-floating gate. Benefiting from the excellent charge trapping capability and strong absorption of the graphdiyne film, as well as the top-floating-gated structure and the ultrathin hBN film used in the device, the optoelectronic memory exhibits high storage performance and robust reliability. A huge difference in the current between the programmed and erased states (>26 µA µm-1 at Vds = 0.1 V) and a prolonged retention time (>105 s) enable the device to achieve multibit storage, for which eight and nine distinct storage levels (3-bit) are obtained by applying periodic gate voltages and optical pulses in the programming and erasing processes, respectively. This work provides an important step toward realizing versatile graphdiyne-based optoelectronic devices in the future.

A gate-tunable symmetric bipolar junction transistor fabricated via femtosecond laser processing.

Two-dimensional (2D) bipolar junction transistors (BJTs) with van der Waals heterostructures play an important role in the development of future nanoelectronics. Herein, a convenient method is introduced for fabricating a symmetric bipolar junction transistor (SBJT), constructed from black phosphorus and MoS2, with femtosecond laser processing. This SBJT exhibits good bidirectional current amplification owing to its symmetric structure. We placed a top gate on one side of the SBJT to change the difference in the major carrier concentration between the emitter and collector in order to further investigate the effects of electrostatic doping on the device performance. The SBJT can also act as a gate-tunable phototransistor with good photodetectivity and photocurrent gain of ß = ∼21. Scanning photocurrent images were used to determine the mechanism governing photocurrent amplification in the phototransistor. These results promote the development of the applications of multifunctional nanoelectronics based on 2D materials.

Exposure Effects of Terahertz Waves on Primary Neurons and Neuron-like Cells Under Nonthermal Conditions.

OBJECTIVE: This study aimed to explore the potential effects of terahertz (THz) waves on primary cultured neurons from 4 rat brain regions (hippocampus, cerebral cortex, cerebellum, and brainstem) and 3 kinds of neuron-like cells (MN9D, PC12, and HT22 cells) under nonthermal conditions. METHODS: THz waves with an output power of 50 (0.16 THz) and 10 (0.17 THz) mW with exposure times of 6 and 60 min were used in this study. Analysis of temperature change, neurite growth, cell membrane roughness, micromorphology, neurotransmitters and synaptic-related proteins (SYN and PSD95) was used to evaluate the potential effects. RESULTS: Temperature increase caused by the THz wave was negligible. THz waves induced significant neurotransmitter changes in primary hippocampal, cerebellar, and brainstem neurons and in MN9D and PC12 cells. THz wave downregulated SYN expression in primary hippocampal neurons and downregulated PSD95 expression in primary cortical neurons. CONCLUSION: Different types of cells responded differently after THz wave exposure, and primary hippocampal and cortical neurons and MN9D cells were relatively sensitive to the THz waves. The biological effects were positively correlated with the exposure time of the THz waves.

A novel microcurrent dressing for wound healing in a rat skin defect model.

BACKGROUND: The exogenous application of low-intensity electric stimulation (ES) may mimic a natural endogenous bioelectric current and accelerate the repair process of skin wounds. This study designed a novel microcurrent dressing (MCD) and evaluated its potential effects on wound healing in a rat skin defect model. METHODS: First, wireless ES was integrated into a medical cotton cushion to fabricate the MCD, and its electrical property was examined by using a universal power meter. Then, animal experiments were conducted to evaluate the MCD's effect. Forty-five rats were randomized into control (Con) group, Vaseline gauze (VG) group and MCD group. A full-thickness round skin incision 1.5 cm in diameter was made on the back of each animal. Apart from routine disinfection, the Con rats were untreated, whereas the other two groups were treated with VG or MCD. On days 3, 7 and 14 post injury, the wound areas were observed and measured using image analysis software following photography, and the skin samples were harvested from wound tissue. Then, histopathological morphology was observed routinely by hematoxylin and eosin (HE) staining; tumor necrosis factor α (TNF-α) and interleukin (IL)-1ß expression were detected by Western blotting. Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) expression were detected with immunohistochemistry. RESULTS: The MCD generated a sf electric potential greater than 0.95 V. Animal experiments showed that the wound-healing rate in the MCD group was significantly increased compared with the Con and VG groups (P < 0.05 or P < 0.01). Histopathological observation revealed an alleviated inflammatory response, induced vascular proliferation and accelerated epithelization in the MCD group. Moreover, samples from the MCD group expressed reduced TNF-α and IL-1ß levels and increased VEGF and EGF levels compared with those of the other two groups (P < 0.05 or P < 0.01). However, no significant difference was noted between the Con and VG groups at each time point. CONCLUSIONS: The MCD generates a stable and lasting ES and significantly promotes wound healing by reducing inflammation duration and increasing growth factors expression. Thus, MCD may act as a promising biomaterial device for skin wound healing.

Behavioral Abnormality along with NMDAR-related CREB Suppression in Rat Hippocampus after Shortwave Exposure.

OBJECTIVE: To estimate the detrimental effects of shortwave exposure on rat hippocampal structure and function and explore the underlying mechanisms. METHODS: One hundred Wistar rats were randomly divided into four groups (25 rats per group) and exposed to 27 MHz continuous shortwave at a power density of 5, 10, or 30 mW/cm2 for 6 min once only or underwent sham exposure for the control. The spatial learning and memory, electroencephalogram (EEG), hippocampal structure and Nissl bodies were analysed. Furthermore, the expressions of N-methyl-D-aspartate receptor (NMDAR) subunits (NR1, NR2A, and NR2B), cAMP responsive element-binding protein (CREB) and phosphorylated CREB (p-CREB) in hippocampal tissue were analysed on 1, 7, and 14 days after exposure. RESULTS: The rats in the 10 and 30 mW/cm2 groups had poor learning and memory, disrupted EEG oscillations, and injured hippocampal structures, including hippocampal neurons degeneration, mitochondria cavitation and blood capillaries swelling. The Nissl body content was also reduced in the exposure groups. Moreover, the hippocampal tissue in the 30 mW/cm2 group had increased expressions of NR2A and NR2B and decreased levels of CREB and p-CREB. CONCLUSION: Shortwave exposure (27 MHz, with an average power density of 10 and 30 mW/cm2) impaired rats' spatial learning and memory and caused a series of dose-dependent pathophysiological changes. Moreover, NMDAR-related CREB pathway suppression might be involved in shortwave-induced structural and functional impairments in the rat hippocampus.

HIF-1α regulates COXIV subunits, a potential mechanism of self-protective response to microwave induced mitochondrial damages in neurons.

Anxiety and speculation about potential health hazards of microwaves exposure are spreading in the past decades. Hypoxia-inducible factor-1α (HIF-1α), which can be activated by reactive oxygen species (ROS), played pivotal roles in protective responses against microwave in neuron-like cells. In this study, we established 30 mW/cm2 microwave exposed animal model, which could result in revisable injuries of neuronal mitochondria, including ultrastructure and functions, such as ROS generation and cytochrome c oxidase (COX) activity. We found that the ratio of COXIV-1/COXIV-2, two isoforms of COXIV, decreased at 1 d and increased from 3 d to 14 d. Similar expression changes of HIF-1α suggested that COXIV-1 and COXIV-2 might be regulated by HIF-1α. In neuron-like cells, 30 mW/cm2 microwave down-regulated COX activity from 30 min to 6 h, and then started to recover. And, both HIF-1α transcriptional activity and COXIV-1/COXIV-2 ratio were up-regulated at 6 h and 9 h after exposure. Moreover, HIF-1α inhibition down-regulated COXIV-1 expression, promoted ROS generation, impaired mitochondrial membrane potentials (MMP), as well as abolished microwave induced ATP production. In conclusion, microwave induced mitochondrial ROS production activated HIF-1α and regulated COXIV-1 expression to restore mitochondria functions. Therefore, HIF-1α might be a potential target to impair microwave induced injuries.

Microwave radiation leading to shrinkage of dendritic spines in hippocampal neurons mediated by SNK-SPAR pathway.

The popularization of microwave raised concerns about its influence on health including cognitive function which is associated greatly with dendritic spines plasticity. SNK-SPAR is a molecular pathway for neuronal homeostatic plasticity during chronically elevated activity. In this study, Wistar rats were exposed to microwaves (30 mW/cm2 for 6 min, 3 times/week for 6 weeks). Spatial learning and memory function, distribution of dendritic spines, ultrastructure of the neurons and their dendritic spines in hippocampus as well as the related critical molecules of SNK-SPAR pathway were examined at different time points after microwave exposure. There was deficiency in spatial learning and memory in rats, loss of spines in granule cells and shrinkage of mature spines in pyramidal cells, accompanied with alteration of ultrastructure of hippocampus neurons. After exposure to 30 mW/cm2 microwave radiation, the up-regulated SNK induced decrease of SPAR and PSD-95, which was thought to cause the changes mentioned above. In conclusion, the microwave radiation led to shrinkage and even loss of dendritic spines in hippocampus by SNK-SPAR pathway, resulting in the cognitive impairments.

Microwave exposure impairs synaptic plasticity in the rat hippocampus and PC12 cells through over-activation of the NMDA receptor signaling pathway.

OBJECTIVE: The aim of this study is to investigate whether microwave exposure would affect the N-methyl-D-aspartate receptor (NMDAR) signaling pathway to establish whether this plays a role in synaptic plasticity impairment. METHODS: 48 male Wistar rats were exposed to 30 mW/cm2 microwave for 10 min every other day for three times. Hippocampal structure was observed through H&E staining and transmission electron microscope. PC12 cells were exposed to 30 mW/cm2 microwave for 5 min and the synapse morphology was visualized with scanning electron microscope and atomic force microscope. The release of amino acid neurotransmitters and calcium influx were detected. The expressions of several key NMDAR signaling molecules were evaluated. RESULTS: Microwave exposure caused injury in rat hippocampal structure and PC12 cells, especially the structure and quantity of synapses. The ratio of glutamic acid and gamma-aminobutyric acid neurotransmitters was increased and the intracellular calcium level was elevated in PC12 cells. A significant change in NMDAR subunits (NR1, NR2A, and NR2B) and related signaling molecules (Ca2+/calmodulin-dependent kinase II gamma and phosphorylated cAMP-response element binding protein) were examined. CONCLUSION: 30 mW/cm2 microwave exposure resulted in alterations of synaptic structure, amino acid neurotransmitter release and calcium influx. NMDAR signaling molecules were closely associated with impaired synaptic plasticity.

Pathological changes in the sinoatrial node tissues of rats caused by pulsed microwave exposure.

To observe microwave induced dynamic pathological changes in the sinus nodes, wistar rats were exposed to 0, 5, 10, 50 mW/cm2 microwave. In 10 and 50 mW/cm2 groups, disorganized sinoatrial node cells, cell swelling, cytoplasmic condensation, nuclear pyknosis, and anachromasis, swollen, and empty mitochondria, and blurred and focally dissolved myofibrils could be detected from 1 to 28 d, while reduced parenchymal cells, increased collagen fibers, and extracellular matrix remodeling of interstitial cells were observed from 6 to 12 months. In conclusion, 10 and 50 mW/cm2 microwave could cause structural damages in the sinoatrial node and extracellular matrix remodeling in rats.

Activation of VEGF/Flk-1-ERK Pathway Induced Blood-Brain Barrier Injury After Microwave Exposure.

Microwaves have been suggested to induce neuronal injury and increase permeability of the blood-brain barrier (BBB), but the mechanism remains unknown. The role of the vascular endothelial growth factor (VEGF)/Flk-1-Raf/MAPK kinase (MEK)/extracellular-regulated protein kinase (ERK) pathway in structural and functional injury of the blood-brain barrier (BBB) following microwave exposure was examined. An in vitro BBB model composed of the ECV304 cell line and primary rat cerebral astrocytes was exposed to microwave radiation (50 mW/cm(2), 5 min). The structure was observed by scanning electron microscopy (SEM) and the permeability was assessed by measuring transendothelial electrical resistance (TEER) and horseradish peroxidase (HRP) transmission. Activity and expression of VEGF/Flk-1-ERK pathway components and occludin also were examined. Our results showed that microwave radiation caused intercellular tight junctions to broaden and fracture with decreased TEER values and increased HRP permeability. After microwave exposure, activation of the VEGF/Flk-1-ERK pathway and Tyr phosphorylation of occludin were observed, along with down-regulated expression and interaction of occludin with zonula occludens-1 (ZO-1). After Flk-1 (SU5416) and MEK1/2 (U0126) inhibitors were used, the structure and function of the BBB were recovered. The increase in expression of ERK signal transduction molecules was muted, while the expression and the activity of occludin were accelerated, as well as the interactions of occludin with p-ERK and ZO-1 following microwave radiation. Thus, microwave radiation may induce BBB damage by activating the VEGF/Flk-1-ERK pathway, enhancing Tyr phosphorylation of occludin, while partially inhibiting expression and interaction of occludin with ZO-1.

AduoLa Fuzhenglin down-regulates microwave-induced expression of ß1-adrenergic receptor and muscarinic type 2 acetylcholine receptor in myocardial cells of rats.

This paper is aimed to study the effect of ADL on expression of ß1-AR and M2-AchR in myocardial cells of rats exposed to microwave radiation. Immunohistochemistry, Western blot and image analysis were used to detect the expression of ß1-AR and M2-AchR in myocardial cells at 7 and 14 d after microwave exposure. The results show that the expression level was higher in microwave exposure group and 0.75 g/(kg•d) ADL group than in sham operation group and significantly lower in 1.5 and 3.0 g/(kg•d) ADL groups than in microwave group. So we have a conclusion that the expression of ß1-AR and M2-AchR is down-regulated in myocardial cells of rats exposed to microwave radiation. ADL can protect rats against microwave-induced heart tissue injury.