Metal Nanogap Memory: Performances and Switching Mechanism.

The nanogap memory (NGM) device, emerging as a promising nonvolatile memory candidate, has attracted increasing attention for its simple structure, nano/atomic scale size, elevated operating speed, and robustness to high temperatures. In this study, nanogap memories based on Pd, Au, and Pt were fabricated by combining nanofabrication with electromigration technology. Subsequent evaluations of the electrical characteristics were conducted under ambient air or vacuum conditions at room temperature. The investigation unveiled persistent challenges associated with metal NGM devices, including (1) prolonged SET operation time in comparison to RESET, (2) the potential generation of error bits when enhancing switching speeds, and (3) susceptibility to degradation during program/erase cycles. While these issues have been encountered by predecessors in NGM device development, the underlying causes have remained elusive. Employing molecular dynamics (MD) simulation, we have, for the first time, unveiled the dynamic processes of NGM devices during both SET and RESET operations. The MD simulation highlights that the adjustment of the tunneling gap spacing in nanogap memory primarily occurs through atomic migration or field evaporation. This dynamic process enables the device to transition between the high-resistance state (HRS) and the low-resistance state (LRS). The identified mechanism provides insight into the origins of the aforementioned challenges. Furthermore, the study proposes an effective method to enhance the endurance of NGM devices based on the elucidated mechanism.

Hierarchical Macroporous Agarose Materials with Polyethyleneimine-Assisted Multiple Boronate Affinity Binding Sites for the Separation of Neomycin.

Quantification of neomycin residues in food samples demands an efficient purification platform. Herein, hierarchical macroporous agarose monoliths with multiple boronate affinity sites were established for selective separation of neomycin. The silica core was synthesized by "one-step" Stöber procedures followed by modification with amino group and incorporation of polyethyleneimine. A versatile macroporous agarose monolith was prepared by emulsification strategies and functionalized with epoxy groups. After introducing polyethyleneimine-integrated silica nanoparticles onto the agarose monolith, fluorophenylboronic acids were immobilized. The physical and chemical characteristics of the composite monolith were analyzed systematically. After optimization, neomycin showed high binding ability of 23.69 mg/g, and the binding capacity can be manipulated by changing the pH and adding monosaccharides. The composite monolith was subsequently utilized to purify neomycin from the spiked model aquatic products followed by high-performance liquid chromatography analysis, which revealed a remarkable neomycin purification effect, indicating the great potential in the separation of neomycin from complicated aquatic products.

Low-temperature resin embedding of the whole brain for various precise structures dissection.

Resin embedding combined with ultra-thin sectioning has been widely used in microscopic and electron imaging to acquire precise structural information of biological tissues. However, the existing embedding method was detrimental to quenchable fluorescent signals of precise structures and pH-insensitive fluorescent dyes. Here, we developed a low-temperature chemical polymerization method named HM20-T to maintain weak signals of various precise structures and to decrease background fluorescence. The fluorescence preservation ratio of green fluorescent protein (GFP) tagged presynaptic elements and tdTomato labeled axons doubled. The HM20-T method was suitable for a variety of fluorescent dyes, such as DyLight 488 conjugated Lycopersicon esculentum lectin. Moreover, the brains also retained immunoreactivity after embedding. In summary, the HM20-T method was suitable for the characterization of multi-color labeled precise structures, which would contribute to the acquisition of complete morphology of various biological tissues and to the investigation of composition and circuit connection in the whole brain.

Learning-Based Near-Infrared Band Simulation with Applications on Large-Scale Landcover Classification.

Multispectral sensors are important instruments for Earth observation. In remote sensing applications, the near-infrared (NIR) band, together with the visible spectrum (RGB), provide abundant information about ground objects. However, the NIR band is typically not available on low-cost camera systems, which presents challenges for the vegetation extraction. To this end, this paper presents a conditional generative adversarial network (cGAN) method to simulate the NIR band from RGB bands of Sentinel-2 multispectral data. We adapt a robust loss function and a structural similarity index loss (SSIM) in addition to the GAN loss to improve the model performance. With 45,529 multi-seasonal test images across the globe, the simulated NIR band had a mean absolute error of 0.02378 and an SSIM of 89.98%. A rule-based landcover classification using the simulated normalized difference vegetation index (NDVI) achieved a Jaccard score of 89.50%. The evaluation metrics demonstrated the versatility of the learning-based paradigm in remote sensing applications. Our simulation approach is flexible and can be easily adapted to other spectral bands.

Preparation of nickel-chelated iminodiacetate-functionalized macroporous agarose monolith using modular and clickable building blocks for affinity separation of histidine-tagged recombinant proteins.

Selective separation and purification of protein from complex medium is required to completely investigate the structure and function of the target protein. In this study, a composite macroporous agarose monolith containing iminodiacetate-chelated Ni2+ ligands was synthesized for selective separation and purification of histidine-tagged recombinant proteins. The large and interconnected pores in the monolith enabled fast binding of proteins with high matrix tolerance in treating complex mediums. To realize the selective protein binding, the iminodiacetate was directly conjugated to epoxy-functionalized agarose monolith via simple chemical reactions between epoxy and imino groups. After chelated Ni2+, the composite monolith could bind histidine-tagged recombinant proteins through the coordination interaction between transition metal ions and the imidazole ring of histidine. To further increase the binding capacities of the monolith, a hydrophilic intermediate polymer chain containing multiple iminodiacetate immobilization sites was conjugated to the azide-functionalized agarose monolith via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The morphology and chemical composition of the composite agarose monolith were characterized systematically. The protein binding capacities of the obtained composite agarose monolith were subsequently investigated. The binding capacities of the composite agarose monolith towards the model proteins Gp10 and Lys84 were 0.93 and 0.51 mg/mL, respectively. The protein binding of the composite agarose monolith could be manipulated by adjusting the temperature and concentrations of imidazole. These results demonstrate that the composite agarose monolith could be used as an affinity medium for rapid separation and purification of histidine-tagged recombinant proteins from biological samples.

Dissection of the long-range projections of specific neurons at the synaptic level in the whole mouse brain.

Through synaptic connections, long-range circuits transmit information among neurons and connect different brain regions to form functional motifs and execute specific functions. Tracing the synaptic distribution of specific neurons requires submicron-level resolution information. However, it is a great challenge to map the synaptic terminals completely because these fine structures span multiple regions, even in the whole brain. Here, we develop a pipeline including viral tracing, sample embedding, fluorescent micro-optical sectional tomography, and big data processing. We mapped the whole-brain distribution and architecture of long projections of the parvalbumin neurons in the basal forebrain at the synaptic level. These neurons send massive projections to multiple downstream regions with subregional preference. With three-dimensional reconstruction in the targeted areas, we found that synaptic degeneration was inconsistent with the accumulation of amyloid-ß plaques but was preferred in memory-related circuits, such as hippocampal formation and thalamus, but not in most hypothalamic nuclei in 8-month-old mice with five familial Alzheimer's disease mutations. Our pipeline provides a platform for generating a whole-brain atlas of cell-type-specific synaptic terminals in the physiological and pathological brain, which can provide an important resource for the study of the organizational logic of specific neural circuits and the circuitry changes in pathological conditions.

Plastic embedding for precise imaging of large-scale biological tissues labeled with multiple fluorescent dyes and proteins.

Resin embedding of multi-color labeled whole organs is the primary step to preserve structural information for visualization of fine structures in three dimensions. It is essential to study the morphological characteristics, spatial and positional relationships of the millions of neurons, and the intricate network of blood vessels with fluorescent labels in the brain. However, the current resin embedding method is inadequate because of incompatibilities with fluorescent dyes, making it difficult to reconstruct a variety of structures for the interpretation of their complex spatial relationships. We modified the resin embedding method for large biological tissues labeled with multiple fluorescent dyes and proteins through different labeling strategies. With TrueBlack as the background fluorescence inhibitor in the glycol methacrylate (GMA) embedding, we referred to the method as GMA-T (Glycol methacrylate with TB). In the GMA-T embedded mouse brains, structures labeled with fluorescent proteins and dyes were visualized in millimeter-scale networks with sub-cellular resolution, allowing quantitative analysis of different anatomical structures in the same brain, including neurons and blood vessels. In combination with high-resolution whole-brain imaging, it is possible to obtain a variety of fluorescence labeled structures in just a few days. We quantified the distribution and morphology of the tdTomato-labeled vasoactive intestinal polypeptide (VIP) neurons and the BSA-FITC labeled blood vessels in the same brain. These results demonstrated that VIP neurons and blood vessels have their own unique distribution patterns and morphological characteristics among cortical regions and different layers in cerebral cortex, and there was no significant correlation between VIP neurons and vessels. This approach provides a novel approach to study the interaction among different anatomical structures within large-volume biological samples labeled with multiple fluorescent dyes and proteins, which helps elucidating the complex anatomical characteristics of biological organs.

Whole-Brain Three-Dimensional Profiling Reveals Brain Region Specific Axon Vulnerability in 5xFAD Mouse Model.

Axonopathy is a pathological feature observed in both Alzheimer's disease (AD) patients and animal models. However, identifying the temporal and regional progression of axonopathy during AD development remains elusive. Using the fluorescence micro-optical sectioning tomography system, we acquired whole-brain datasets in the early stage of 5xFAD/Thy1-GFP-M mice. We reported that among GFP labeled axons, GFP-positive axonopathy first formed in the lateral septal nucleus, subiculum, and medial mammillary nucleus. The axonopathy further increased in most brain regions during aging. However, most of the axonopathic varicosities disappeared significantly in the medial mammillary nucleus after 8 weeks old. Continuous three-dimensional datasets showed that axonopathy in the medial mammillary nucleus was mainly located on axons from hippocampal GFP-positive neurons. Using the rabies viral tracer in combination with immunohistochemistry, we found that axons in the medial mammillary nucleus from the subiculum were susceptible to lesions that prior to the occurrence of behavioral disorders. In conclusion, we created an early-stage spatiotemporal map of axonopathy in 5xFAD/Thy1-GFP-M mice and identified specific neural circuits which are vulnerable to axon lesions in an AD mouse model. These findings underline the importance of early interventions for AD, and may contribute to the understanding of its progression and its early symptom treatment.

Multi-objective collaborative optimization strategy for efficiency and chromaticity of stratified OLEDs based on an optical simulation method and sensitivity analysis.

The low efficiency and dissatisfactory chromaticity remain as important challenges on the road to the OLED commercialization. In this paper, we propose a multi-objective collaborative optimization strategy to simultaneously improve the efficiency and ameliorate the chromaticity of the stratified OLED devices. Based on the formulations derived for the current efficiency and the chromaticity Commission International de L'Eclairage (CIE) of OLEDs, an optical sensitivity model is presented to quantitatively analyze the influence of the layer thickness on the current efficiency and the CIE. Subsequently, an evaluation function is defined to effectively balance the current efficiency as well as the CIE, and a collaborative optimization strategy is further proposed to simultaneously improve both of them. Simulations are comprehensively performed on a typical top-emitting blue OLED to demonstrate the necessity and the effectivity of the proposed strategy. The influences of the layer thickness incorporated in the blue OLED are ranked based on the sensitivity analysis method, and by optimizing the relative sensitive layer thicknesses in the optical views, a 16% improvement can be achieved for the current efficiency of the OLED with desired CIE meantime. Hence, the proposed multi-objective collaborative optimization strategy can be well applied to design high-performance OLED devices by improving the efficiency without chromaticity quality degradation.

Long-range inputome of cortical neurons containing corticotropin-releasing hormone.

Dissection of the neural circuits of the cerebral cortex is essential for studying mechanisms underlying brain function. Herein, combining a retrograde rabies tracing system with fluorescent micro-optical sectional tomography, we investigated long-range input neurons of corticotropin-releasing hormone containing neurons in the six main cortical areas, including the prefrontal, somatosensory, motor, auditory, and visual cortices. The whole brain distribution of input neurons showed similar patterns to input neurons distributed mainly in the adjacent cortical areas, thalamus, and basal forebrain. Reconstruction of continuous three-dimensional datasets showed the anterior and middle thalamus projected mainly to the rostral cortex whereas the posterior and lateral projected to the caudal cortex. In the basal forebrain, immunohistochemical staining showed these cortical areas received afferent information from cholinergic neurons in the substantia innominata and lateral globus pallidus, whereas cholinergic neurons in the diagonal band nucleus projected strongly to the prefrontal and visual cortex. Additionally, dense neurons in the zona incerta and ventral hippocampus were found to project to the prefrontal cortex. These results showed general patterns of cortical input circuits and unique connection patterns of each individual area, allowing for valuable comparisons among the organisation of different cortical areas and new insight into cortical functions.

Solvent-Free Alcoholysis of Tripalmitin to Produce 2-Monoglyceride as Precursor for 1, 3-Oleoyl-2-Palmitoylglycerol.

2-monoglyceride (2-MAG) was essential to produce high purity of 1, 3-Oleoyl-2-palmitoylglycerol (OPO), an important infant formula additive. Traditional synthesis of 2-MAG requires chemical solvent to solve the high melting point substrate, yielding the risk of solvent residue in OPO. This paper developed a solvent-free synthesis route of 2-MAG by alcoholysis of high melting point tripalmitin (PPP). Ethyl palmitate (EP), one of the reaction byproducts, was added in the beginning of alcoholysis process to promote the solubleness of high melting point PPP, avoiding the addition of toxic chemical solvent. The product of alcoholysis was separated by two-step molecular distillations. Separated DAG was used to produce 2-MAG and the final conversion of 2-MAG reached about 85.90%, with the purity of 92.36%. 2-MAG was trans-esterified to OPO with ethyl oleate, and the yield of OPO was up to 85.06% with 80.17% palmitic acid located on sn-2 position. The solvent-free synthesis route avoids the usage of hazardous chemical solvents, providing safer infant formula additive.

Whole Brain Mapping of Long-Range Direct Input to Glutamatergic and GABAergic Neurons in Motor Cortex.

Long-range neuronal circuits play an important role in motor and sensory information processing. Determining direct synaptic inputs of excited and inhibited neurons is important for understanding the circuit mechanisms involved in regulating movement. Here, we used the monosynaptic rabies tracing technique, combined with fluorescent micro-optical sectional tomography, to characterize the brain-wide input to the motor cortex (MC). The whole brain dataset showed that the main excited and inhibited neurons in the MC received inputs from similar brain regions with a quantitative difference. With 3D reconstruction we found that the distribution of input neurons, that target the primary and secondary MC, had different patterns. In the cortex, the neurons projecting to the primary MC mainly distributed in the lateral and anterior portion, while those to the secondary MC distributed in the medial and posterior portion. The input neurons in the subcortical areas also showed the topographic shift model, as in the thalamus, the neurons distributed as outer and inner shells while the neurons in the claustrum and amygdala were in the ventral and dorsal part, respectively. These results lay the anatomical foundation to understanding the organized pattern of motor circuits and the functional differences between the primary and secondary MC.

A Core-Shell Structured Immobilized Lipase and Its Application in High-Temperature Reactions.

In this research, a core-shell immobilized lipase was constructed with the cost-effective bamboo carrier. Natural bamboo powder was pretreated by different methods. The results of SEM and BET demonstrated that alkali pretreatment increased the surface roughness with formed wrinkles and micropores, facilitating the lipase adsorption on the pretreated carrier. The optimal immobilization conditions were obtained through the response surface method, and the optimized conditions were 2 wt% sodium hydroxide solution, 1.2 wt% sodium alginate, and 0.69 wt% calcium chloride at a calcification time of 100 min. Under this condition, the immobilized lipase showed an excellent protein adsorption rate and thermal stability. When the core-shell structured immobilized lipase was used in wax ester synthesis system, the esterification yield (80%) did not show an obvious decline after 17 batches. The results indicated that the core-shell immobilized lipase is effective for the biocatalytic reaction, and the immobilization method is a promising strategy for future enzyme immobilization and modification in industrial applications.

Simultaneous Acquisition of Multicolor Information From Neural Circuits in Resin-Embedded Samples.

Resin embedding has been widely used for precise imaging of fluorescently labeled biological samples with optical and electron microscopy. The low preservation rate of fluorescence, especially for red fluorescent proteins, has limited the application of resin embedding in multifluorescent protein-labeled samples. Here, we optimized the embedding method to retain the intensity of multiple fluorescent proteins during resin embedding. By reducing the polymerization temperature from 50 to 35°C and adding a fluorescent protein protection reagent during the embedding process, we successfully increased the fluorescence preservation rate by nearly twofold for red fluorescent proteins, including tdTomato, mCherry, and DsRed. Meanwhile, the background fluorescence decreased significantly in the optimized embedding method. This method is suitable not only for red fluorescent protein-labeled samples but also for blue (BFP) and green fluorescent protein (GFP)-labeled samples. We embedded brains labeled with BFP, DsRed, and GFP via AAV and rabies virus and acquired the distribution of input neurons to different cortical areas. With GFP/tdTomato double-labeled samples in resin, we obtained the cholinergic projectome of the pedunculopontine tegmental nucleus (PPTg) and the distribution of cholinergic neurons at single-neuron resolution in the whole brain simultaneously. Input cholinergic terminals from the PPTg were found to innervate the cholinergic soma and fiber in the neocortex, basal forebrain and brainstem, indicating that local cholinergic neurons received long-range cholinergic modulation from the midbrain. Our optimized method is useful for embedding multicolor fluorescent protein-labeled samples to acquire multidimensional structural information on neural circuits at single-neuron resolution in the whole brain.

Optimization of Melanin Extraction from the Wood Ear Medicinal Mushroom, Auricularia auricula-judae (Agaricomycetes), by Response Surface Methodology and Its Antioxidant Activities In Vitro.

The optimal conditions for melanin extraction from Auricularia auricula-judae (Hei 29) fruiting bodies was determined on the basis of the extract yield of melanin, calculated by using a single-factor experiment and response surface methodology. Its antioxidant activities were also studied in vitro. Various optimal process conditions for melanin extraction were determined by using Design-Expert software: incubation temperature, 69.11°C; incubation time, 58.66 minutes; and incubation pH, 12.81. Under these conditions, the melanin yield was 2.59%. We found that the antioxidant activities of A. auricula-judae melanin in vitro were strong against DPPH radicals and superoxide anions. The rate of DPPH radical scavenging was 63.04% when the A. auricula-judae melanin concentration was 0.36 mg/mL; the rate of superoxide anion scavenging reached 39.79% when the concentration was 0.375 mg/mL. However, the antioxidant activity against hydroxyl radicals was somewhat weak; the rate of scavenging reached only 7.47% when the A. auricula-judae melanin concentration was 0.06 mg/mL.