Label- and slide-free tissue histology using 3D epi-mode quantitative phase imaging and virtual H&E staining.

Histological staining of tissue biopsies, especially hematoxylin and eosin (H&E) staining, serves as the benchmark for disease diagnosis and comprehensive clinical assessment of tissue. However, the process is laborious and time-consuming, often limiting its usage in crucial applications such as surgical margin assessment. To address these challenges, we combine an emerging 3D quantitative phase imaging technology, termed quantitative oblique back illumination microscopy (qOBM), with an unsupervised generative adversarial network pipeline to map qOBM phase images of unaltered thick tissues (i.e., label- and slide-free) to virtually stained H&E-like (vH&E) images. We demonstrate that the approach achieves high-fidelity conversions to H&E with subcellular detail using fresh tissue specimens from mouse liver, rat gliosarcoma, and human gliomas. We also show that the framework directly enables additional capabilities such as H&E-like contrast for volumetric imaging. The quality and fidelity of the vH&E images are validated using both a neural network classifier trained on real H&E images and tested on virtual H&E images, and a user study with neuropathologists. Given its simple and low-cost embodiment and ability to provide real-time feedback in vivo, this deep learning-enabled qOBM approach could enable new workflows for histopathology with the potential to significantly save time, labor, and costs in cancer screening, detection, treatment guidance, and more.

Ultra-High Sensitivity Terahertz Microstructured Fiber Biosensor for Diabetes Mellitus and Coronary Heart Disease Marker Detection.

Diabetes Mellitus (DM) and Coronary Heart Disease (CHD) are among top causes of patient health issues and fatalities in many countries. At present, terahertz biosensors have been widely used to detect chronic diseases because of their accurate detection, fast operation, flexible design and easy fabrication. In this paper, a Zeonex-based microstructured fiber (MSF) biosensor is proposed for detecting DM and CHD markers by adopting a terahertz time-domain spectroscopy system. A suspended hollow-core structure with a square core and a hexagonal cladding is used, which enhances the interaction of terahertz waves with targeted markers and reduces the loss. This work focuses on simulating the transmission performance of the proposed MSF sensor by using a finite element method and incorporating a perfectly matched layer as the absorption boundary. The simulation results show that this MSF biosensor exhibits an ultra-high relative sensitivity, especially up to 100.35% at 2.2THz, when detecting DM and CHD markers. Furthermore, for different concentrations of disease markers, the MSF exhibits significant differences in effective material loss, which can effectively improve clinical diagnostic accuracy and clearly distinguish the extent of the disease. This MSF biosensor is simple to fabricate by 3D printing and extrusion technologies, and is expected to provide a convenient and capable tool for rapid biomedical diagnosis.

Optimization of a flexible fiber-optic probe for epi-mode quantitative phase imaging.

Quantitative oblique back-illumination microscopy (qOBM) is an emerging label-free optical imaging technology that enables 3D, tomographic quantitative phase imaging (QPI) with epi-illumination in thick scattering samples. In this work, we present a robust optimization of a flexible, fiber-optic-based qOBM system. Our approach enables in silico optimization of the phase signal-to-noise-ratio over a wide parameter space and obviates the need for tedious experimental optimization which could easily miss optimal conditions. Experimental validations of the simulations are also presented and sensitivity limits for the probe are assessed. The optimized probe is light-weight (∼40g) and compact (8mm in diameter) and achieves a 2µm lateral resolution, 6µm axial resolution, and a 300µm field of view, with near video-rate operation (10Hz, limited by the camera). The phase sensitivity is <20nm for a single qOBM acquisition (at 10Hz) and a lower limit of ∼3 nm via multi-frame averaging. Finally, to demonstrate the utility of the optimized probe, we image (1) thick, fixed rat brain samples from a 9L gliosarcoma tumor model and (2) freshly excised human brain tissues from neurosurgery. Acquired qOBM images using the flexible fiber-optic probe are in excellent agreement with those from a free-space qOBM system (both in-situ), as well as with gold-standard histopathology slices (after tissue processing).

Simple single-shot complete spatiotemporal intensity and phase measurement of an arbitrary ultrashort pulse using coherent modulation imaging.

We propose a simple single-shot spatiotemporal measurement technique called coherent modulation imaging for the spatio-spectrum (CMISS), which reconstructs the full three-dimensional high-resolution characteristics of ultrashort pulses based on frequency-space division and coherent modulation imaging. We demonstrated it experimentally by measuring the spatiotemporal amplitude and phase of a single pulse with a spatial resolution of 44 µm and a phase accuracy of 0.04 rad. CMISS has good potential for high-power ultrashort-pulse laser facilities and can measure even spatiotemporally complicated pulses with important applications.

Regulation of Cytosolic pH: The Contributions of Plant Plasma Membrane H+-ATPases and Multiple Transporters.

Cytosolic pH homeostasis is a precondition for the normal growth and stress responses in plants, and H+ flux across the plasma membrane is essential for cytoplasmic pH control. Hence, this review focuses on seven types of proteins that possess direct H+ transport activity, namely, H+-ATPase, NHX, CHX, AMT, NRT, PHT, and KT/HAK/KUP, to summarize their plasma-membrane-located family members, the effect of corresponding gene knockout and/or overexpression on cytosolic pH, the H+ transport pathway, and their functional regulation by the extracellular/cytosolic pH. In general, H+-ATPases mediate H+ extrusion, whereas most members of other six proteins mediate H+ influx, thus contributing to cytosolic pH homeostasis by directly modulating H+ flux across the plasma membrane. The fact that some AMTs/NRTs mediate H+-coupled substrate influx, whereas other intra-family members facilitate H+-uncoupled substrate transport, demonstrates that not all plasma membrane transporters possess H+-coupled substrate transport mechanisms, and using the transport mechanism of a protein to represent the case of the entire family is not suitable. The transport activity of these proteins is regulated by extracellular and/or cytosolic pH, with different structural bases for H+ transfer among these seven types of proteins. Notably, intra-family members possess distinct pH regulatory characterization and underlying residues for H+ transfer. This review is anticipated to facilitate the understanding of the molecular basis for cytosolic pH homeostasis. Despite this progress, the strategy of their cooperation for cytosolic pH homeostasis needs further investigation.

2D van der Waals materials for ultrafast pulsed fiber lasers: review and prospect.

2D van der Waals materials are crystals composed of atomic layers, which have atomic thickness scale layers and rich distinct properties, including ultrafast optical response, surface effects, light-mater interaction, small size effects, quantum effects and macro quantum tunnel effects. With the exploration of saturable absorption characteristic of 2D van der Waals materials, a series of potential applications of 2D van der Waals materials as high threshold, broadband and fast response saturable absorbers (SAs) in ultrafast photonics have been proposed and confirmed. Herein, the photoelectric characteristics, nonlinear characteristic measurement technique of 2D van der Waals materials and the preparation technology of SAs are systematically described. Furthermore, the ultrafast pulsed fiber lasers based on classical 2D van der Waals materials including graphene, transition metal chalcogenides, topological insulators and black phosphorus have been fully summarized and analyzed. On this basis, opportunities and directions in this field, as well as the research results of ultrafast pulsed fiber lasers based on the latest 2D van der Waals materials (such as PbO, FePSe3, graphdiyne, bismuthene, Ag2S and MXene etc), are reviewed and summarized.

Label-free detection of brain tumors in a 9L gliosarcoma rat model using stimulated Raman scattering-spectroscopic optical coherence tomography.

SIGNIFICANCE: In neurosurgery, it is essential to differentiate between tumor and healthy brain regions to maximize tumor resection while minimizing damage to vital healthy brain tissue. However, conventional intraoperative imaging tools used to guide neurosurgery are often unable to distinguish tumor margins, particularly in infiltrative tumor regions and low-grade gliomas. AIM: The aim of this work is to assess the feasibility of a label-free molecular imaging tool called stimulated Raman scattering-spectroscopic optical coherence tomography (SRS-SOCT) to differentiate between healthy brain tissue and tumor based on (1) structural biomarkers derived from the decay rate of signals as a function of depth and (2) molecular biomarkers based on relative differences in lipid and protein composition extracted from the SRS signals. APPROACH: SRS-SOCT combines the molecular sensitivity of SRS (based on vibrational spectroscopy) with the spatial and spectral multiplexing capabilities of SOCT to enable fast, spatially and spectrally resolved molecular imaging. SRS-SOCT is applied to image a 9L gliosarcoma rat tumor model, a well-characterized model that recapitulates human high-grade gliomas, including high proliferative capability, high vascularization, and infiltration at the margin. Structural and biochemical signatures acquired from SRS-SOCT are extracted to identify healthy and tumor tissues. RESULTS: Data show that SRS-SOCT provides light-scattering-based signatures that correlate with the presence of tumors, similar to conventional OCT. Further, nonlinear phase changes from the SRS interaction, as measured with SRS-SOCT, provide an additional measure to clearly separate tumor tissue from healthy brain regions. We also show that the nonlinear phase signals in SRS-SOCT provide a signal-to-noise advantage over the nonlinear amplitude signals for identifying tumors. CONCLUSIONS: SRS-SOCT can distinguish both spatial and spectral features that identify tumor regions in the 9L gliosarcoma rat model. This tool provides fast, label-free, nondestructive, and spatially resolved molecular information that, with future development, can potentially assist in identifying tumor margins in neurosurgery.

Towards in-vivo label-free detection of brain tumor margins with epi-illumination tomographic quantitative phase imaging.

Brain tumor surgery involves a delicate balance between maximizing the extent of tumor resection while minimizing damage to healthy brain tissue that is vital for neurological function. However, differentiating between tumor, particularly infiltrative disease, and healthy brain in-vivo remains a significant clinical challenge. Here we demonstrate that quantitative oblique back illumination microscopy (qOBM)-a novel label-free optical imaging technique that achieves tomographic quantitative phase imaging in thick scattering samples-clearly differentiates between healthy brain tissue and tumor, including infiltrative disease. Data from a bulk and infiltrative brain tumor animal model show that qOBM enables quantitative phase imaging of thick fresh brain tissues with remarkable cellular and subcellular detail that closely resembles histopathology using hematoxylin and eosin (H&E) stained fixed tissue sections, the gold standard for cancer detection. Quantitative biophysical features are also extracted from qOBM which yield robust surrogate biomarkers of disease that enable (1) automated tumor and margin detection with high sensitivity and specificity and (2) facile visualization of tumor regions. Finally, we develop a low-cost, flexible, fiber-based handheld qOBM device which brings this technology one step closer to in-vivo clinical use. This work has significant implications for guiding neurosurgery by paving the way for a tool that delivers real-time, label-free, in-vivo brain tumor margin detection.

Long noncoding RNA KTN1 antisense RNA 1exerts an oncogenic function in lung adenocarcinoma by regulating DEP domain containing 1 expression via activating epithelial-mesenchymal transition.

Long noncoding RNA (lncRNA) KTN1 antisense RNA 1 (KTN1-AS1) is a novel promoter in the progression of some cancers. However, the knowledge of its role in lung adenocarcinoma is still limited. The current study aimed to examine the biological functions of KTN1-AS1 and its coexpressed protein in lung adenocarcinoma. The RNA sequencing expression profiles from The Cancer Genome Atlas (TCGA) database were downloaded to evaluate the expression of KTN1-AS1 and its coexpressed protein, as well as assess their prognostic values. The correlation between DEP domain containing 1 (DEPDC1) and KTN1-AS1 levels was verified using Pearson's correlation coefficient. Real-time qPCR and western blot were adopted to determine the mRNA and protein levels of the corresponding molecules. Cell viability, invasiveness and motility were assayed by cell counting kit-8, clone formation and Transwell assays, appropriately. High levels of KTN1-AS1 were observed and led to a poorer prognosis in lung adenocarcinoma patients, according to the public dataset. DEPDC1 was found to be a downstream protein associated with KTN1-AS1. Moreover, DEPDC1 was also upregulated in lung adenocarcinoma tissues and can be seen as an independent prognosticator for patients with lung adenocarcinoma. Besides, DEPDC1 expression was positively correlated with KTN1-AS1 expression, which was verified by real-time qPCR and western blot. Functional experiments indicated that KTN1-AS1-knockdown inhibited cells proliferation, migration and invasion, whereas DEPDC1-overexpression could diminish this inhibition. Conversely, overexpression of KTN1-AS1 presented a promoting effect on these phenotypes, whereas silencing DEPDC1 could reduce these accelerations. Further evidence supported that KTN1-AS1/DEPDC1 plays the carcinogenic role by activating the epithelial-mesenchymal transition process and elevating MMP9 expression in lung adenocarcinoma cells. These data suggested that the KTN1-AS1/DEPDC1 axis may involve in the tumorigenesis in lung adenocarcinoma by activating the epithelial-mesenchymal transition process.

Arbuscular mycorrhizal fungus-mediated amelioration of NO2-induced phytotoxicity in tomato.

Atmospheric nitrogen dioxide (NO2) negatively affects plant (crop) growth and development, as well the yield and quality in some regions or environments. Arbuscular mycorrhizal fungus (AMF)-mediated amelioration of NO2-induced plant damage has been reported, but the underlying mechanisms remained unclear. This study explored the beneficial effect of AMF symbiosis on tomato plant responses to NO2 at physiology, biochemistry, and gene expression, with an emphasis on nitrate metabolism, antioxidative defense, and photosynthetic performance. Pot-grown plants were used in the experiments, which were performed in laboratory from February to November 2019. NO2 fumigation with a dose of 10 ± 1 ppm was carried out after 50 d of plant growth, and data were collected following 8 h of fumigation. NO2 fumigation (+NO2) and AMF inoculation (+AMF), alone and especially in combination (NO2 + AMF), increased the gene expression of nitrate- and nitrite reductase, and their enzymatic activity in leaves, such as by 61%, 27%, and 126% for the activity of nitrate reductase, and by 95%, 37%, and 188% for nitrite reductase, respectively, in +NO2, +AMF, and AMF + NO2 plants relative the control (-NO2, -AMF) levels. Following NO2 exposure, +AMF leaves displayed stronger activities of superoxide dismutase, peroxidase and catalase, and higher content of glutathione and ratio of its reduced form to oxidized form, as compared with -AMF ones. Correspondingly, lesser oxidative damage was detected in +AMF than in -AMF plants, as indicated by the contents of H2O2 and malondialdehyde, electrolyte leakage, also by in situ visualization for the formation of H2O2, superoxide anion, and dead cells. The increased antioxidative capacity in +AMF plants was correlated with enhanced expression of antioxidation-related genes. Exposure to NO2 substantially impaired photosynthetic processes in both + AMF and -AMF plants, but an obvious mitigation was observed in the former than in the latter. For example, the total chlorophyll, net photosynthetic rate, stomatal conductance, and ribulose-1,5-bisphosphate carboxylase activity were 18%, 27%, 26%, and 40% higher, respectively, in +AMF than in -AMF plants under NO2 stress. The differential photosynthetic performance was also revealed by chlorophyll fluorescence imaging. We analyzed the expression patterns of some genes related to photosynthesis and carbon metabolisms, and found that all of them exclusively presented a higher expression level in +AMF plants relative to -AMF ones under NO2 stress. Taken together, this study provided evidence that AMF symbiosis played a positively regulatory role in host plant responses to NO2, probably by increasing leaf nitrate metabolism and antioxidative defense, and maintaining the photosynthetic efficiency to some extent, wherein the transcription regulation might be a main target.

Synthesis and antitumor activity of α,ß-unsaturated carbonyl moiety- containing oleanolic acid derivatives targeting PI3K/AKT/mTOR signaling pathway.

Oleanolic acid (OA) and its semi-synthetic derivatives have been reported to have a wide range of biological activities. The introduction of electrophilic Michael acceptor group can increase the reactivity of OA to cellular targets and thus improve the anti-tumor activity. In this work, a series of novel α,ß-unsaturated carbonyl derivatives of OA were designed and synthesized. Their in vitro cytotoxic activity against MCF-7, HepG2 and HeLa cells were tested. Most derivatives exhibited improved cell growth inhibitory activity, especially for 3d with an IC50 of 0.77 µM in MCF-7 cells. Moreover, 3d inhibited the migration of MCF-7 and HeLa cells at the concentration of 4 µM. Flow cytometric analysis revealed that 3d induced cell apoptosis and S phase arrest in a concentration-dependent manner. Western blotting experiment demonstrated that 3d inhibited the phosphorylation of AKT and mTOR. These results suggest that this series of OA derivatives bearing exocyclic methylene ketone pharmacophore are promising anticancer agents as potential PI3K/AKT/mTOR pathway inhibitors.

Ethylene insensitive mutation improves Arabidopsis plant tolerance to NO2 exposure.

Ethylene signaling was addressed, for the first time, in plant responses to nitrogen dioxide (NO2) by comparatively analyzing the performance of Arabidopsis ethylene insensitive 2 (ein2-1) with wild-type (WT) plants. Following NO2 fumigation, severe leaf wilting and chlorosis occurred in WT plants, but much less symptoms were observed in ein2-1. The activities of superoxide dismutase (SOD), peroxidase (PRX) and catalase (CAT) were 39%, 92%, and 11% higher, respectively, in ein2-1 than in WT following NO2 exposure. Although glutathione contents and the ratio of its reduced form (GSH) to oxidized form (GSSG) were decreased by NO2, an obviously alleviated degree was detected in ein2-1 relative to WT. Correspondingly, the contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA), and electrolyte leakage were 25%, 24%, and 29% lower, respectively, in ein2-1 than in WT. The difference of oxidative stress between two tested genotypes was also revealed by the leaf staining regarding the production and distribution of H2O2, superoxide anion (O2˙-), and cell death. The genes involved in antioxidation or oxidation-reduction processes mostly presented a stronger expression in ein2-1 than in WT under NO2 stress. The photosynthesis-related parameters including chlorophyll and soluble sugar contents, net photosynthetic rate (Pn), and ribulose bisphosphate carboxylase/oxygenase (Rubisco) activity and gene expression, and chlorophyll fluorescence parameters were affected, generally, to a lesser degree in ein2-1 than in WT following NO2 fumigation. The enzymatic activities and gene expressions of invertases mostly displayed a higher level in ein2-1 relative to WT following NO2 fumigation. For example, the activities of cytoplasmic, cell wall and vacuolar invertases were 76%, 26%, and 26% higher, respectively, in ein2-1 than in WT. Together, these data suggest that ethylene signal insensitivity efficiently improves plant tolerance to NO2 exposure, and the possible mechanisms might be correlated with leaf antioxidative defense, photosynthesis-related processes, and sucrose metabolisms.

Orobanone analogues from acid-promoted aromatization rearrangement of curcumol inhibit hypoxia-inducible factor-1 (HIF-1) in cell-based reporter assays.

In this paper, the mechanism of orobanone analogues formation via aromatization rearrangement of curcumol was minutely explored. Aromatization of curcumol with acetone under acidic condition was selected as the model reaction. The formation of a stable aromatic system was the driving force for this reaction. Based on the model reaction, other four new orobanone analogues were prepared through curcumol reacting with different carbonyl compounds. The results showed that the stability of carbocation, which was generated from the carbonyl compounds, and the steric hindrance were main factors affecting the aromatization. We also synthesized the analogue of aromaticane B using compound 2. In vitro anti-proliferative activity of some derivatives were tested by MTT assay. Two derivatives showed weak anti-tumor effect on two cancer cell lines (HepG2 and MCF7) under normoxia. Four orobanone analogue 2, 5, 6 and 9 significantly inhibited hypoxia-induced HIF-1 luciferase reporter activity in HeLa cells with the IC50 values of 13.6, 6.6, 2.4 and 18.2 µM, respectively.

Salicylic acid-altering Arabidopsis plant response to cadmium exposure: Underlying mechanisms affecting antioxidation and photosynthesis-related processes.

Previous studies have demonstrated that the genetic modification of basal salicylic acid (SA) level changed Arabidopsis plant response to cadmium (Cd) stress, but the mechanisms remain evaluated. In this study, Arabidopsis wild type (WT) and its SA-reducing transgenic line nahG (naphthalene hydroxylase G), SA-accumulating mutant snc1 (suppressor of nonexpressor of PR gene, constitutive 1) were exposed to 50 µM Cd2+ for 48 h or 7 d (just for assessing plant growth). The Cd treatment increased the expression levels of SA biosynthesis-related genes leading to enhanced SA accumulations in plant leaves, which was further confirmed by the expression patterns of SA marker genes. Cadmium accumulation was much higher in the Cd-exposed roots than in leaves, but was not affected by SA levels. Exposure to Cd inhibited plant growth of both aerial parts and roots, to a greater degree in snc1, and a lesser extent in nahG as compared with WT. Although Cd treatment increased plant antioxidative capacity, oxidative damage happened, especially to snc1 plants. Photoinhibition occurred in Cd-stressed plants leading to a decrease in photosynthetic activity, with a greater degree in snc1, while a lesser in nahG, as indicated by the changes of several key photosynthetic parameters. We comprehensively analyzed the expression profiles of photosynthesis-related genes, and observed a positive correlation between Cd tolerance and gene expression levels, wherein the transcription levels of two electron transport-related genes and two amylase-encoding genes were all up-regulated in nahG plants after Cd treatment, implying a significance of the related processes in this genotype against Cd stress.

Latent Sex Differences in Molecular Signaling That Underlies Excitatory Synaptic Potentiation in the Hippocampus.

Excitatory synapses can be potentiated by chemical neuromodulators, including 17ß-estradiol (E2), or patterns of synaptic activation, as in long-term potentiation (LTP). Here, we investigated kinases and calcium sources required for acute E2-induced synaptic potentiation in the hippocampus of each sex and tested whether sex differences in kinase signaling extend to LTP. We recorded EPSCs from CA1 pyramidal cells in hippocampal slices from adult rats and used specific inhibitors of kinases and calcium sources. This revealed that, although E2 potentiates synapses to the same degree in each sex, cAMP-activated protein kinase (PKA) is required to initiate potentiation only in females. In contrast, mitogen-activated protein kinase, Src tyrosine kinase, and rho-associated kinase are required for initiation in both sexes; similarly, Ca2+/calmodulin-activated kinase II is required for expression/maintenance of E2-induced potentiation in both sexes. Calcium source experiments showed that L-type calcium channels and calcium release from internal stores are both required for E2-induced potentiation in females, whereas in males, either L-type calcium channel activation or calcium release from stores is sufficient to permit potentiation. To investigate the generalizability of a sex difference in the requirement for PKA in synaptic potentiation, we tested how PKA inhibition affects LTP. This showed that, although the magnitude of both high-frequency stimulation-induced and pairing-induced LTP is the same between sexes, PKA is required for LTP in females but not males. These results demonstrate latent sex differences in mechanisms of synaptic potentiation in which distinct molecular signaling converges to common functional endpoints in males and females.SIGNIFICANCE STATEMENT Chemical- and activity-dependent neuromodulation alters synaptic strength in both male and female brains, yet few studies have compared mechanisms of neuromodulation between the sexes. Here, we studied molecular signaling that underlies estrogen-induced and activity-dependent potentiation of excitatory synapses in the hippocampus. We found that, despite similar magnitude increases in synaptic strength in males and females, the roles of cAMP-regulated protein kinase, internal calcium stores, and L-type calcium channels differ between the sexes. Therefore, latent sex differences in which the same outcome is achieved through distinct underlying mechanisms in males and females include kinase and calcium signaling involved in synaptic potentiation, demonstrating that sex is an important factor in identification of molecular targets for therapeutic development based on mechanisms of neuromodulation.

Coupling ultrafast laser pulses into few-mode optical fibers: a numerical study of the spatiotemporal field coupling efficiency.

Few-mode optical fibers have been widely used in applications such as data transmission and laser amplification. The coupling of laser beams into such fibers is important because it determines the fiber mode contents, which influence the beam quality, laser amplification efficiency, and appropriate distortion control methods. Ultrafast lasers, as a widely used type of laser source for intense-field applications, can generate pulses with broad spectra and varying phases, adding complexity to the fiber mode coupling problem. In this paper, we numerically study the coupling performance of ultrafast laser pulses into few-mode fibers, investigating the mode coupling efficiency under different launching field conditions. Certain modes can be optimized with their coupling efficiencies in the presence of pulse spatiotemporal couplings, which provides a new perspective toward generating complex waveforms and studying laser matter interactions.

α2-Adrenergic receptor activation promotes long-term potentiation at excitatory synapses in the mouse accessory olfactory bulb.

The formation of mate recognition memory in mice is associated with neural changes at the reciprocal dendrodendritic synapses between glutamatergic mitral cell (MC) projection neurons and GABAergic granule cell (GC) interneurons in the accessory olfactory bulb (AOB). Although noradrenaline (NA) plays a critical role in the formation of the memory, the mechanism by which it exerts this effect remains unclear. Here we used extracellular field potential and whole-cell patch-clamp recordings to assess the actions of bath-applied NA (10 µM) on the glutamatergic transmission and its plasticity at the MC-to-GC synapse in the AOB. Stimulation (400 stimuli) of MC axons at 10 Hz but not at 100 Hz effectively induced N-methyl-d-aspartate (NMDA) receptor-dependent long-term potentiation (LTP), which exhibited reversibility. NA paired with subthreshold 10-Hz stimulation (200 stimuli) facilitated the induction of NMDA receptor-dependent LTP via the activation of α2-adrenergic receptors (ARs). We next examined how NA, acting at α2-ARs, facilitates LTP induction. In terms of acute actions, NA suppressed GC excitatory postsynaptic current (EPSC) responses to single pulse stimulation of MC axons by reducing glutamate release from MCs via G-protein coupled inhibition of calcium channels. Consequently, NA reduced recurrent inhibition of MCs, resulting in the enhancement of evoked EPSCs and spike fidelity in GCs during the 10-Hz stimulation used to induce LTP. These results suggest that NA, acting at α2-ARs, facilitates the induction of NMDA receptor-dependent LTP at the MC-to-GC synapse by shifting its threshold through disinhibition of MCs.

Selenium and Zinc against Aß25-35-Induced Cytotoxicity and Tau Phosphorylation in PC12 Cells and Inhibits γ-cleavage of APP.

Amyloid beta (Aß) is the main component of the amyloid plaques that accumulate in the brains of Alzheimer patients. The present study was conducted to investigate whether the combined treatment with selenium (Se) and zinc (Zn) offers more beneficial effects than that provided by either of them alone in reversing Aß25-35-induced neurotoxicity in PC12 cells. Cells were pretreated with 0.1 µmol/L of Se and Zn for 4 h, after treated with 10 mmol/L Aß25-35 for 24 h. Cells were divided into control and five treated groups, and received either 10 mmol/L Aß25-35,10 mmol/L Aß25-35 + 0.1 µmol/L Se, 10 mmol/L Aß25-35 + 0.1 µmol/L Zn, 10 mmol/LAß25-35 + 0.1 µmol/L Se + 0.1 µmol/L Zn, or 0.1 µmol/L Se + 0.1 µmol/L Zn. The result showed that cell viability was decreased in MTT metabolic rate; LDH release and MDA, H2O2, and NO levels were increased and the GSK-3ß and phosphorylated tau protein level were increased in Aß25-35-treated group (P < 0.05 or P < 0.01), which whole changes were attenuated by Se and Zn and Se combined Zn. In order to evaluate whether the Se and Zn have an effect on processing pathway of amyloid precursor protein (APP), we examined the activity of γ-secretase in primary cultured cortical neuron cells. ELISA analysis showed that Se and Zn could inhibit the activity of γ-secretase. Then we also investigated the effect of Se and Zn on the Aß1-40 concentration and APP-N-terminal fragment expression from APP695 stably transfected Chinese hamster ovary (CHO) cells. APP695 stably transfected CHO cells were treated with 0.1 µmol/L Se and Zn; cells were divided into control and four treated groups, which received either 0.5 M DAPT, 0.1 µmol/L Se, 0.1 µmol/L Zn, or 0.1 µmol/L Se + 0.1 µmol/L Zn. Se and Zn could decrease Aß1-40 production and increase the APP-N-terminal fragment protein expression. These experiments indicate that Se and Zn have a protective effect on AD pathology that a possible mechanism is inhibiting the activity of γ-secretase to decreasing Aß1-40 production further influencing the APP processing. Altogether, our findings may provide a novel therapeutic target to treat AD sufferers.

Visualizing spatiotemporal pulse propagation: first-order spatiotemporal couplings in laser pulses.

Even though a general theory of first-order spatiotemporal couplings exists in the literature, it is often difficult to visualize how these distortions affect laser pulses. In particular, it is difficult to show the spatiotemporal phase of pulses in a meaningful way. Here, we propose a general solution to plotting the electric fields of pulses in three-dimensional space that intuitively shows the effects of spatiotemporal phases. The temporal phase information is color-coded using spectrograms and color response functions, and the beam is propagated to show the spatial phase evolution. Using this plotting technique, we generate two- and three-dimensional images and movies that show the effects of spatiotemporal couplings.

Measuring spatiotemporal ultrafast field structures of pulses from multimode optical fibers.

Ultrashort pulses emerging from multimode optical fibers are spatiotemporally complex, because inside these fibers the modes have different spatial intensity patterns and experience different propagation velocities and dispersions. To determine the spatiotemporal field from multimode fibers, we applied a technique for the complete measurement of the output pulses called a spatially and temporally resolved intensity and phase evaluation device: full information from a single hologram. It yields the complete electric field over space and time from multiple digital holograms, simultaneously recorded at different frequencies on a single camera frame. Using femtosecond pulses from a Ti:sapphire laser, we measured the first few linearly polarized modes (LP01, LP11, LP02, and LP21) inside several few-mode fibers. We also generate movies displaying the measured spatial, temporal, and spectral field features.