Distinct roles of excitatory and inhibitory neurons in the medial prefrontal cortex in the expression and reconsolidation of methamphetamine-associated memory in male mice.

Methamphetamine, a commonly abused drug, is known for its high relapse rate. The persistence of addictive memories associated with methamphetamine poses a significant challenge in preventing relapse. Memory retrieval and subsequent reconsolidation provide an opportunity to disrupt addictive memories. However, the key node in the brain network involved in methamphetamine-associated memory retrieval has not been clearly defined. In this study, using the conditioned place preference in male mice, whole brain c-FOS mapping and functional connectivity analysis, together with chemogenetic manipulations of neural circuits, we identified the medial prefrontal cortex (mPFC) as a critical hub that integrates inputs from the retrosplenial cortex and the ventral tegmental area to support both the expression and reconsolidation of methamphetamine-associated memory during its retrieval. Surprisingly, with further cell-type specific analysis and manipulation, we also observed that methamphetamine-associated memory retrieval activated inhibitory neurons in the mPFC to facilitate memory reconsolidation, while suppressing excitatory neurons to aid memory expression. These findings provide novel insights into the neural circuits and cellular mechanisms involved in the retrieval process of addictive memories. They suggest that targeting the balance between excitation and inhibition in the mPFC during memory retrieval could be a promising treatment strategy to prevent relapse in methamphetamine addiction.

mGluR5 in amygdala modulates fear memory generalization.

Introduction: Fear memory generalization is regarded as the core characteristic of posttraumatic stress disorder (PTSD) development. However, the mechanism that contributes to the generalization of conditioned fear memory is still unclear. The generalization is generally considered to be a mismatch that occurs during memory consolidation. Methods: Foot shocks and tones were given as unconditioned stress and conditioned stress, respectively for fear conditioning training. Immunofluorescence staining, western blotting and qPCR were performed to determine the expression of different genes in amygdala of mice after fear conditioning training. Cycloheximide was used as a protein synthesis inhibitor and 2-methyl-6-phenylethynyl-pyridine was injected for mGluR5 inhibition. Results: Fear conditioning using caused incremental generalization, which was clearly observed during training. The density of c-Fos+ cells or the synaptic p-NMDAR expression did not differ with stress intensities. Strong-shock fear conditioning could induce significant mGluR5 de novo synthesis in the amygdala, which was not observed in the weak-shock group. Inhibition of mGluR5 impaired fear memory generalization induced by strong-shock fear conditioning, but the generalization level induced by weak-shock training was enhanced. Discussion: These results indicated that mGluR5 in the amygdala is critical to the function of inappropriate fear memory generalization and suggested that this may be a potential target for the treatment of PTSD.

National IoMT platform strategy portfolio decision model under the COVID-19 environment: based on the financial and non-financial value view.

The Internet of Medical Things (IoMT) is an emerging technology in the healthcare revolution which provides real-time healthcare information communication and reasonable medical resource allocation. The COVID-19 pandemic has had a significant effect on people's lives and has affected healthcare capacities. It is important for integrated IoMT platform development to overcome the global pandemic challenges. This study proposed the national IoMT platform strategy portfolio decision-making model from the non-financial (technology, organization, environment) and financial perspectives. As a solution to the decision problem, initially, the decision-making trial and evaluation laboratory (DEMATEL) technology were employed to capture the cause-effect relationship based on the perspectives and criteria obtained from the insight of an expert team. The analytic network process (ANP) and pairwise comparisons were then used to determine the weights for the strategy. Simultaneously, this study incorporated IoMT platform resource limitations into the zero-one goal programming (ZOGP) method to obtain an optimal portfolio selection for IoMT platform strategy planning. The results showed that the integrated MCDM method produced reasonable results for selecting the most appropriate IoMT platform strategy portfolio when considering resource constraints such as system installation costs, consultant fees, infrastructure costs, reduction of medical staff demand, and improvement rates for diagnosis efficiency. The decision-making model of the IoMT platform in this study was conclusive and significantly compelling to aid government decision makers in concentrating their efforts on planning IoMT strategies in response to various pandemic and medical resource allocations.

Fabrication of single Ga-doped ZnS nanowires as high-gain photosensors by focused ion beam deposition.

ZnS nanowires were synthesized via a vapor-liquid-solid mechanism and then fabricated into a single-nanowire field-effect transistor by focused ion beam (FIB) deposition. The field-effect electrical properties of the FIB-fabricated ZnS nanowire device, namely conductivity, mobility and hole concentration, were 9.13 Ω-1 cm-1, 13.14 cm2 V-1 s-1and 4.27 × 1018 cm-3, respectively. The photoresponse properties of the ZnS nanowires were studied and the current responsivity, current gain, response time and recovery time were 4.97 × 106 A W-1, 2.43 × 107, 9 s and 24 s, respectively. Temperature-dependent I-V measurements were used to analyze the interfacial barrier height between ZnS and the FIB-deposited Pt electrode. The results show that the interfacial barrier height is as low as 40 meV. The energy-dispersive spectrometer elemental line scan shows the influence of Ga ions on the ZnS nanowire surface on the FIB-deposited Pt contact electrodes. The results of temperature-dependent I-V measurements and the elemental line scan indicate that Ga ions were doped into the ZnS nanowire, reducing the barrier height between the FIB-deposited Pt electrodes and the single ZnS nanowire. The small barrier height results in the FIB-fabricated ZnS nanowire device acting as a high-gain photosensor.

Electrical and Optical Properties of Au-Catalyzed GaAs Nanowires Grown on Si (111) Substrate by Molecular Beam Epitaxy.

In this study, defect-free zinc blende GaAs nanowires on Si (111) by molecular beam epitaxy (MBE) growth are systematically studied through Au-assisted vapor-liquid-solid (VLS) method. The morphology, density, and crystal structure of GaAs nanowires were investigated as a function of substrate temperature, growth time, and As/Ga flux ratio during MBE growth, as well as the thickness, annealing time, and annealing temperature of Au film using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), cathodoluminescence (CL), and Raman spectroscopy. When the As/Ga flux ratio is fixed at 25 and the growth temperature at 540 °C, the GaAs nanowires exhibit a defect-free zinc blende structure with uniform and straight morphology. According to the characteristics of GaAs nanowires grown under varied conditions, a growth mechanism for defect-free zinc blende GaAs nanowires via Au-assisted vapor-liquid-solid (VLS) method is proposed. Finally, doping by Si and Be of nanowires is investigated. The results of doping lead to GaAs nanowires processing n-type and p-type semiconductor properties and reduced electrical resistivity. This study of defect-free zinc blende GaAs nanowire growth should be of assistance in further growth and applications studies of complex III-V group nanostructures.

Detection of electrically neutral and nonpolar molecules in ionic solutions using silicon nanowires.

We report on a technique that can extend the use of nanowire sensors to the detection of interactions involving nonpolar and neutral molecules in an ionic solution environment. This technique makes use of the fact that molecular interactions result in a change in the permittivity of the molecules involved. For the interactions taking place at the surface of nanowires, this permittivity change can be determined from the analysis of the measured complex impedance of the nanowire. To demonstrate this technique, histidine was detected using different charge polarities controlled by the pH value of the solution. This included the detection of electrically neutral histidine at a sensitivity of 1 pM. Furthermore, it is shown that nonpolar molecules, such as hexane, can also be detected. The technique is applicable to the use of nanowires with and without a surface-insulating oxide. We show that information about the changes in amplitude and the phase of the complex impedance reveals the fundamental characteristics of the molecular interactions, including the molecular field and the permittivity.

Isolation and Identification of Post-Transcriptional Gene Silencing-Related Micro-RNAs by Functionalized Silicon Nanowire Field-effect Transistor.

Many transcribed RNAs are non-coding RNAs, including microRNAs (miRNAs), which bind to complementary sequences on messenger RNAs to regulate the translation efficacy. Therefore, identifying the miRNAs expressed in cells/organisms aids in understanding genetic control in cells/organisms. In this report, we determined the binding of oligonucleotides to a receptor-modified silicon nanowire field-effect transistor (SiNW-FET) by monitoring the changes in conductance of the SiNW-FET. We first modified a SiNW-FET with a DNA probe to directly and selectively detect the complementary miRNA in cell lysates. This SiNW-FET device has 7-fold higher sensitivity than reverse transcription-quantitative polymerase chain reaction in detecting the corresponding miRNA. Next, we anchored viral p19 proteins, which bind the double-strand small RNAs (ds-sRNAs), on the SiNW-FET. By perfusing the device with synthesized ds-sRNAs of different pairing statuses, the dissociation constants revealed that the nucleotides at the 3'-overhangs and pairings at the terminus are important for the interactions. After perfusing the total RNA mixture extracted from Nicotiana benthamiana across the device, this device could enrich the ds-sRNAs for sequence analysis. Finally, this bionanoelectronic SiNW-FET, which is able to isolate and identify the interacting protein-RNA, adds an additional tool in genomic technology for the future study of direct biomolecular interactions.

Polymer-free patterning of graphene at sub-10-nm scale by low-energy repetitive electron beam.

A polymer-free technique for generating nanopatterns on both synthesized and exfoliated graphene sheets is proposed and demonstrated. A low-energy (5-30 keV) scanning electron beam with variable repetition rates is used to etch suspended and unsuspended graphene sheets on designed locations. The patterning mechanisms involve a defect-induced knockout process in the initial etching stage and a heat-induced curling process in a later stage. Rough pattern edges appear due to inevitable stochastic knockout of carbon atoms or graphene structure imperfection and can be smoothed by thermal annealing. By using this technique, the minimum feature sizes achieved are about 5 nm for suspended and 7 nm for unsuspended graphene. This study demonstrates a polymer-free direct nanopatterning approach for graphene.

Extract of Ginkgo biloba EGb761 facilitates extinction of conditioned fear measured by fear-potentiated startle.

A standard extract of Ginkgo biloba (EGb761) has been used in the treatment of various common geriatric complaints including vertigo, short-term memory loss, hearing loss, lack of attention, or vigilance. We demonstrated that acute systemic administration of EGb761 facilitated the acquisition of conditioned fear. Many studies suggest the neural mechanism underlies extinction is similar to the acquisition. This raises a possibility that EGb761 may modulate and accelerate the fear extinction process. We tested this possibility by using fear-potentiated startle (FPS) on laboratory rats. Acute systemic injection of EGb761 (10, 20, or 50 mg/kg) 30 min before extinction training facilitated extinction in a dose-dependent manner. Intra-amygdaloid infusion of EGb761 (28 ng/side, bilaterally) 10 min before extinction training also facilitated extinction. Control experiments showed that facilitation effect of EGb761 was not the result of impaired expression of conditioned fear or accelerated forgetting. Rats previously injected with EGb761 showed significant FPS after retraining. Extinction of conditioned fear appeared to result from acute drug effects rather than from toxic action. Systemic administration of EGb761 immediately after extinction training did not facilitate extinction, suggested the EGb761 facilitation effect is contributed to the acquisition phase of extinction learning. Western blot results showed that extinction induced amygdaloid extracellular signal-regulated kinase (ERK1/2) phosphorylation was significantly elevated by EGb761 treatment. Intra-amygdala injection of ERK1/2 inhibitor PD98059 completely blocked the EGb761 effect. Therefore, acute EGb761 administration modulated extinction of conditioned fear by activating ERK1/2.

Extract of Ginkgo biloba EGb 761 facilitates fear conditioning measured by fear-potentiated startle.

Extract of Ginkgo biloba EGb 761 has been used in the treatment of various common geriatric complaints including vertigo, short-term memory loss, hearing loss, lack of attention, vigilance and cerebral vascular disorder. Recent results suggest that it can serve as a cognitive enhancer and anti-stress buffer. It raises a possibility that EGb 761 may be involved in the fear conditioning. In this study, we used fear-potentiated startle (FPS) to evaluate the possible effects of EGb 761 on the acquisition stage of fear conditioning. Our results showed that administration of EGb 761 30 min prior to the conditioning facilitated acquisition of conditioned fear in a dose dependent manner. No significant differences had been observed in either basal startle response or shock activity. These results indicated that the facilitation effect of EGb 761 was not the result of impaired basal startle response or enhanced pain perception. Subsequent control experiment results indicated that the facilitation effect of EGb 761 on the acquisition was not due to anxiogenic effect or non-specific effect. Our data present the first evidence that EGb 761 can enhance fear memory formation rather than serve as an anti-stress buffer.