Projections from anteromedial thalamus nucleus to the midcingulate cortex mediate pain and anxiety-like behaviors in mice.

Prior research has demonstrated the involvement of the midcingulate cortex (MCC) and its downstream pathway in pain regulation. However, the mechanism via which pain information is conveyed to the MCC remains unclear. The present study utilized immunohistochemistry, chemogenetics, optogenetics, and behavior detection methods to explore the involvement of MCC, anteromedial thalamus nucleus (AM), and AM-MCC pathway in pain and emotional regulation. Chemogenetics or optogenetics methods were employed to activate/inhibit MCCCaMKIIα, AMCaMKIIα, AMCaMKIIα-MCC pathway. This manipulation evokes/relieves mechanical and partial heat hyperalgesia, as well as anxiety-like behaviors. In the complete Freund,s adjuvant (CFA) inflammatory pain model, chemogenetic inhibition of the AMCaMKIIα-MCCCaMKIIα pathway contributed to pain relief. Notably, this study presented the first evidence implicating the AM in the regulation of nociception and negative emotions. Additionally, it was observed that the MCC primarily receives projections from the AM, highlighting the crucial role of this pathway in the transmission of pain and emotional information.

Inhibition of oxidative stress by testosterone improves synaptic plasticity in senescence accelerated mice.

It is well known that synaptic plasticity is associated with cognitive performance in Alzheimer's disease (AD). Testosterone (T) is known to exert protective effects on cognitive deficits in AD, but the underlying mechanisms of androgenic action on synaptic plasticity remain unclear. Thus, the aim of this study was to examine the protective mechanism attributed to T on synaptic plasticity in an AD senescence accelerated mouse prone 8 (SAMP8) model. The following parameters were measured: (1) number of intact pyramidal cells in hippocampal CA1 region (2) phosphorylated N-methyl-D-aspartate receptor-1 (p-NMDAR1) and (3) phosphorylated calmodulin-dependent protein kinase II (p-CaMKII). In addition, the content of whole brain malondialdehyde (MDA) as well as activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined. Treatment with T significantly elevated the number of intact pyramidal cells in hippocampal CA1 region and markedly increased hippocampal protein and mRNA expression levels of p-NMDAR1 and p-CaMK II. Further, T significantly decreased whole brain MDA levels accompanied by elevated activities of SOD and GSH-Px. Data suggest that the protective effects of T on synaptic plasticity in a mouse AD model may be associated with reduction of oxidant stress.

The protective mechanisms underlying Ginsenoside Rg1 effects on rat sciatic nerve injury.

Ginsenoside Rg1 (GsRg1), derived from the herb Ginseng, was found to exert protective effects in nerve injury; however, the mechanisms underlying these effects remain to be determined. Oxidant stress and apoptosis are known to be involved in sciatic nerve injury. Thus, the aim of this study was to examine whether GsRg1 was able to modify sciatic nerve injury in a rat model. The following parameters were measured: (1) number of spinal cord motoneurons by Nissl staining, (2) oxidation parameters including spinal cord malondialdehyde (MDA) levels and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as (3) involvement of apoptosis by determining caspase-3 and X-linked inhibitor of apoptosis protein (XIAP) by immunohistochemistry and Western blot. The number of spinal cord motoneurons was significantly reduced after sciatic nerve injury, while treatment with GsRg1 markedly elevated cell number. Sciatic nerve injury markedly increased spinal cord MDA content concomitant with reduced activities of SOD and GSH-Px. GsRg1 significantly decreased MDA content accompanied by elevated activities of SOD and GSH-Px. Further nerve injury significantly diminished protein expression levels of XIAP accompanied by elevated protein expression levels of caspase-3 in the spinal cord. GsRg1 markedly increased protein expression levels of XIAP, but significantly reduced protein expression levels of caspase-3. Data suggest that the protective effects of GsRg1 in sciatic nerve injury may be associated with reduced oxidative stress involving anti-apoptotic pathways.

Protective mechanism of testosterone on cognitive impairment in a rat model of Alzheimer's disease.

Cognitive dysfunction in Alzheimer's disease is strongly associated with a reduction in synaptic plasticity, which may be induced by oxidative stress. Testosterone is beneficial in learning and memory, although the underlying protective mechanism of testosterone on cognitive performance remains unclear. This study explored the protective mechanism of a subcutaneous injection of 0.75 mg testosterone on cognitive dysfunction induced by bilateral injections of amyloid beta 1-42 oligomers into the lateral ventricles of male rats. Morris water maze test results demonstrated that testosterone treatment remarkably reduced escape latency and path length in Alzheimer's disease rat models. During probe trials, testosterone administration significantly elevated the percentage of time spent in the target quadrant and the number of platform crossings. However, flutamide, an androgen receptor antagonist, inhibited the protective effect of testosterone on cognitive performance in Alzheimer's disease rat models. Nissl staining, immunohistochemistry, western blot assay, and enzyme-linked immunosorbent assay results showed that the number of intact hippocampal pyramidal cells, the dendritic spine density in the hippocampal CA1 region, the immune response and expression level of postsynaptic density protein 95 in the hippocampus, and the activities of superoxide dismutase and glutathione peroxidase were increased with testosterone treatment. In contrast, testosterone treatment reduced malondialdehyde levels. Flutamide inhibited the effects of testosterone on all of these indicators. Our data showed that the protective effect of testosterone on cognitive dysfunction in Alzheimer's disease is mediated via androgen receptors to scavenge free radicals, thereby enhancing synaptic plasticity.

The protective mechanism underlying phenylethanoid glycosides (PHG) actions on synaptic plasticity in rat Alzheimer's disease model induced by beta amyloid 1-42.

Phenylethanoid glycosides (PHG), derived from Herba cistanche, were found to exert protective effects on cognitive dysfunctions by improving synaptic plasticity in Alzheimer's disease (AD) rat model. However, the mechanisms underlying these effects of PHG on synaptic plasticity remain to be determined. Thus the aim of this study was to examine the influence of PHG on synaptic plasticity in male AD rat model induced by bilateral central nervous system ventricle injections of beta amyloid 1-42 oligomers (Aß1-42). The following parameters were measured: (1) number of intact pyramidal cells in hippocampal CA1 region by Nissl staining, (2) post synaptic density 95 (PSD-95), phosphorylated N-methyl-D-aspartate receptor-1(p-NMDAR1) and (3) phosphorylated Tau protein (p-Tau) by immunohistochemistry and western blot. In addition, the content of malondialdehyde (MDA) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined. Aß1-42 lowered the number of intact pyramidal cells in hippocampal CA1 region. In contrast, treatment with PHG significantly elevated this cell number. Aß1-42 significantly diminished protein expression levels of PSD-95 accompanied by elevated protein expression levels of p-NMDAR1 and p-Tau. PHG markedly increased protein expression levels of PSD-95, but significantly reduced protein expression levels of p-NMDAR1 and p-Tau. Further, Aß1-42 markedly increased MDA content concomitantly with reduced activities of SOD and GSH-Px. PHG significantly decreased MDA content accompanied by elevated activities of SOD and GSH-Px. Data suggest that the protective effects of PHG on synaptic plasticity may involve inhibition of cytotoxicity-mediated by Aß-1-42 administration and reduction of oxidant stress.

Investigation on the effect of output mirror transmission in WS2-based red-light passively Q-switched Pr:ZBLAN all-fiber lasers.

We report the experimental investigation of visible passively Q-switched Pr3+-doped all-fiber lasers with tungsten disulfide (WS2) saturable absorber, where red-light short-pulse generations from different output mirror transmissions are systemically characterized. The proposed simple and compact all-fiber linear cavity was constructed by a fiber-pigtail-based blue laser-diode pump, a Pr3+-doped fluorozirconate glass active fiber, and the fiber end-facet mirrors. Integrating a free-standing layered WS2 film into the laser cavity initiated the Q-switching operation. Stable microsecond-duration output pulses with kilohertz repetition rates are achieved, corresponding to a few mW/nJ average output power and single-pulse energy. The comparisons on red-light Q-switched output parameters for output transmissions of both ∼40% and ∼80% are performed. This work could provide a useful guideline to manipulate the output performance of visible pulsed all-fiber lasers for various practical applications.

The effects of phenylethanoid glycosides, derived from Herba cistanche, on cognitive deficits and antioxidant activities in male SAMP8 mice.

Cognitive deficits are closely associated with hippocampal synaptic changes. Phenylethanoid glycosides (PhG), derived from Herba cistanche, are known to exert protective effects on cognitive deficits in Alzheimer's disease (AD); however, the underlying mechanisms of this herbal extract on cognitive performance remain unclear. The aim of this study was thus to examine the protective mechanism attributed to PhG on cognitive deficits in an AD senescence accelerated mouse prone 8 (SAMP8) model. Cognitive deficit parameters examined included (1) Morris water maze (MWM) assessing cognitive performance and (2) quantification of dendritic spine density in hippocampal CA1 region by Golgi staining, a molecular biomarker of synaptic function. In addition, levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD) and gluthathione peroxidase (GSH-Px) were determined to examine the potential role of oxidant processes in cognitive dysfunction. Data showed that PhG significantly decreased escape latency and path length, associated with a rise in the percentage of time spent in the target quadrant and number of platform crossings. In addition, PhG significantly increased dendritic spine density in the hippocampal CA1 region accompanied by elevated expression levels of synaptophysin (SYN) and post synaptic density 95 (PSD-95), reduced MDA content, and elevated the activities of SOD and GSH-Px. Data suggest that the ability of PhG to ameliorate cognitive deficits in SAMP8 mice may be related to promotion in synaptic plasticity involving antioxidant processes.

All-fiber passively Q-switched 604 nm praseodymium laser with a Bi2Se3 saturable absorber.

We experimentally demonstrated a simple passively Q-switched praseodymium (Pr3+)-doped all-fiber laser at 604 nm with a Bi2Se3 saturable absorber (SA). A Bi2Se3/polyvinyl alcohol composite film is sandwiched between two ferrules to construct a fiber-compatible Q-switcher. Two fiber end facet mirrors build a compact-linear resonator. The repetition rate of the achieved 604 nm Q-switching pulse can be widely tuned from 86.2 to 187.4 kHz, and the pulse duration can be as narrow as 494 ns. To the best of our knowledge, this is the shortest operation wavelength of a Bi2Se3-based pulsed all-fiber laser at 604 nm.

miR-181 regulation of BAX controls cisplatin sensitivity of prostate cancer cells.

Prostate cancer is one of the most common male malignancies and remains the second leading cause for cancer-specific mortalities in men. Cisplatin is commonly used as a chemotherapeutic agent against advanced cancers, and is now used in metastatic prostate cancers. Cisplatin exerts its cytotoxic effects by cross-linking genomic DNA (gDNA) which induces DNA damage on rapidly dividing cancer cells. However, cisplatin leads to systemic side effects and some patients never respond. Our previous report demonstrated an oncogenic role of miR-181a in human prostate cancer. In this study, we investigate the mechanistic potential of miR-181a in regulating cisplatin sensitivity in this context. We report that cisplatin treatment significantly enhanced miR-181a expression and that exogenous overexpression of miR-181a decreased sensitivity of prostate cancer cells to cisplatin. Additionally, we observed that cisplatin-resistant prostate cancer cells harbored high levels of miR-181a expression. Mechanistically, we demonstrate the pro-apoptotic protein, BAX, is typically enhanced by cisplatin treatment but its suppression promoted resistance. Here we demonstrate miR-181a regulation of BAX was mediated through a complimentary interaction with the 3'UTR of the BAX transcript. We subsequently show that BAX expression restored cisplatin sensitivity in miR-181a overexpressing prostate cancer cells. In parallel, we demonstrate inhibition of miR-181a restored BAX expression as well as cisplatin sensitivity in resistant cells. This study suggests that miR-181a is a potential therapeutic target for prostate cancers that are resistant to cisplatin.

2-Aminoxazole and 2-Aminothiazole Dasatinib Derivatives as Potent Inhibitors of Chronic Myeloid Leukemia K562 Cells.

Dasatinib is an important drug against chronic myeloid leukemia (CML). In this paper, we describe the preparation and anti-CML activity of 2-aminoxazole and 2-aminothiazole dasatinib derivatives. Biological activity was measured by the inhibition of proliferation of human CML K562 cells. The 2-aminoxazole derivatives had similar activities as the 2-aminothiazole derivatives. All newly synthesized compounds demonstrated more potent antiproliferative activity than imatinib. A few compounds (8b, 8c, 9b) showed nanomolar inhibitory activity, similar to that of dasatinib.

Microfluidic fabrication of cholesteric liquid crystal core-shell structures toward magnetically transportable microlasers.

We report a magnetically transportable microlaser with cholesteric liquid crystal (CLC) core-shell structure, operating in band-edge mode. The dye doped CLC shells as a water-in-oil-in-water (W/O/W) double emulsion were fabricated by microfluidics. Water-dispersible Fe3O4 magnetic nanoparticles were incorporated in the inner aqueous phase by taking advantage of the immiscibility with the middle CLC oil phase. The influence of temperature and shell thickness on laser properties was discussed in detail. The non-invasive manipulation of microlasers was realized under a magnetic field. The dependence of velocity on the viscosity of the carrying fluid and size of the core-shell structure was theoretically analyzed and experimentally investigated using a prototype electromagnetic platform. We also discussed the design principles for this type of DDCLC core-shell structure. Such magnetically transportable microlasers offer promise in in-channel illumination applications requiring active control inside micro-channels.

The Role of Nerve Growth Factor in Ginsenoside Rg1-Induced Regeneration of Injured Rat Sciatic Nerve.

Sciatic nerve injury is commonly seen in clinical practice predominantly associated with trauma or sports injuries. Recent studies indicated that ginsenoside Rg1 (Gs Rg1), extracted from Chinese herbs, was found to promote regeneration of injured rat sciatic nerve and that nerve growth factor (NGF) may be involved in this process. The aim of this study was to examine the role that NGF may play in ginsenoside Rg1-induced regeneration of rat sciatic nerve following injury. Animals following surgical right sciatic nerve injury were subsequently administered intraperitoneally either saline (sham control) or different doses of 2, 4, 8, or 12 mg/kg daily GsRg1 for 2 to 8 wk. In addition, 100 µg/kg mecobalamin, a drug utilized to treat nerve injuries, was employed as a positive control. After 2, 4, or 8 wk, sciatic functional index (SFI) and mean nerve conduction velocity (MNCV), markers of sciatic nerve function, were assessed to determine whether recovery of injured sciatic nerve occurred. In addition, immunohistochemistry and Western blot methods were used to examine NGF protein expression changes. Results showed that all doses of GsRg1 significantly increased SFI and MNCV in injured sciatic-nerve-damaged rats in a manner similar to that noted with mecobalamin. It is of interest that the intermediate 4- and 8-mg/kg doses were more effective in restoring nerve functions. Immunohistochemistry and Western blot results also demonstrated a similar pattern with enhanced NGF protein expression at all doses, but greater effects were noted at 4 and 8 mg/kg GsRg1. Data suggest that GsRg1 promotes recovery of injured sciatic nerve functions within a specific dose range and that NGF may be involved in this physiological process.

The Effect of Schizandrol A-Induced DNA Methylation on SH-SY5YAB 1-40 Altered Neuronal Cell Line: A Potential Use in Alzheimer's Disease.

Disturbances in DNA methylation are postulated to result in various central nervous system diseases including Alzheimer's disease (AD). The SH-SY5Y neuronal cell line treated with Aß1-40 (5 µmol/L) protein is considered to be a model of AD. Hence the aim of this study was to examine the influence of Schizandrol A, a plant extract, on DNA methylation in SH-SY5Y cells exposed to Aß1-40. Aß1-40 were incubated with varying concentrations of Sehizandrol A to a final concentration of 1 (low), 3 (intermediate) or 9 µg/ml (high). Exposure of SH-SY5Y with Aß1-40 reduced viability, and altered cellular morphology and mRNA expression of DNA methyltransferase (DNMT3A) and DNMT3B. Treatment with 1 or 3 µg/ml Sehizandrol A resulted in normal cell morphology as well as elevated cell number, enhanced viability, and increased mRNA expression of DNMT3A and DNMT3B compared to saline. However, an increase in Sehizandrol A to 9 µg/ml produced a fall in cell viability, as well as a decrease in mRNA DNMT3A and DNMT3B expression to control levels. Data demonstrated that Schizandrol A at 1 or 3 µg/ml improved cell morphological appearance and viability of Aß1-40 injured SH-SY5Y cells by an enhanced DNA methylation pathway.

Metallically coated dielectric rectangle resonator.

The double transfer matrix method (DTMM) is proposed for calculating the eigenvalues of the resonant mode of a metallically coated dielectric rectangle resonator. Two-dimensional electromagnetic analyses are performed to investigate the optical influences induced by planar structure parameters. The results show that there theoretically exists a highest Q-factor resonance for both TE and TM modes at a certain length-width ratio with fixed resonant wavelength and resonator area. Due to the influence of surface plasma polaritons (SPPs) trapped at the corners of the resonator which is not considered in DTMM, the TM mode resonances are deformed and deviate severely from that of the analytical model. The geometric deformation on the resonator is introduced by replacing the four right angles with circular boundaries, and the SPP accompanied mode behaviors are corrected to the standing waves.

Tailoring the plasmonic whispering gallery modes of a metal-coated resonator for potential application as a refractometric sensor.

Plasmonic whispering gallery (WG) modes confined in metal-coated resonators are theoretically investigated by electromagnetic analyses. The resonance can be tuned from internal surface plasmonic WG modes to the hybrid state of the plasmonic mode by an introduced isolation layer. As the coated metal is reduced in size, the optical resonance is shifted out by the mode coupling of the internal and external surface plasmonic WG modes. Based on the optical leak of the plasmonic WG mode, the optical influences led by the surroundings with a variable refractive index are considered. Device performance criteria such as optical power leak, resonant wavelength shift, and threshold gain are studied. Full wave simulations are also employed and the results present good consistency with analytic solutions. The metal-coated resonator assisted by an active material is expected to provide promising performance as a refractometric sensor.

Optical coupling and emission of metal-insulator confined circular resonators.

We numerically investigate the direct and indirect optical interactions of pair circular resonators laterally confined by metal-insulator waveguide. The direct optical interaction shows the split of quality (Q) factors of bonding and antibonding states only happens for thick insulator. The indirect optical interaction through a waveguide is proposed to control the modes resonance and collect the output emissions. The Q factors of resonant modes versus the coupling distance (width of waveguide) are studied. The results show whispering gallery modes(WGMs) engaged into interaction are strongly coupled with the guided waves of waveguide once its width is close to the cut-off width of guided waves, while the coupled mode of two WGMs is not limited by this condition. High Q factor mode, combined with a robust wide emission waveguide(close to the cut-off width of second-order guided waves), can be realized from the bonding states of WGM and coupled WGM with an added wave envelope in waveguide. In addition to the pair resonators, the studies on four resonators interacted with each other through waveguide are also addressed and wide waveguide output is anticipated.

Optical processing between two metallically hybrid microdisks.

A waveguide is bridged between two metallically hybrid microdisks for achieving nonlocal optical processing. The whispering gallery mode (WGM) is split into two modes, one is intrinsic WGM and the other is oscillating mode (OM) whose photons oscillate between two microdisks through the waveguide. The characteristics of OM on the waveguide's width and length are studied. The results show the fundamental WGM oscillation only happens at certain lengths and widths of the waveguide, and strong optical interaction between two microdisks is accompanied by a high-loss waveguide. The optical processing through a waveguide between two individual resonators or photon producers may be applied to dynamic control on the photon states.

Metallically confined microdisks with in-plane multiple guided emissions.

We theoretically present in-plane multiple guided emissions of metallically confined microdisk lasers which can be applied to drive multiple elements in compact photonic integration at the same time. Two to four-port microdisks with transverse magnetic and electric polarizations are investigated based on finite difference time domain simulation and padé approximation. Modes filtering of coupling ports are verified by the calculated mode quality factors (Q) which are decided by the matching of coupling ports with the energy density distribution of corresponding modes. Single mode lasing operation of semiconductor microdisk with guided emissions is possibly realized by selectively pumping.

Port output of metallo-dielectric confined circular microlasers.

Port output of metallo-dielectric confined circular microlasers directly connected with a coupling waveguide in radial direction is presented and numerically investigated by the finite-difference time-domain method and the Padé approximation. The quality factors of fundamental whispering-gallery modes confined in microlasers with dimensions of around 1 µm do not deteriorate until the output waveguide can support a one-order guided wave. The port-output metallo-dielectric microlasers with low threshold are expected. In addition, the mode characteristics of port-output metallo-dielectric microlasers are studied based on ample modes of larger cavity, where coupled modes and standing-wave-like modes dominate in the cavity with a wide output port.

Study of anomalous infrared properties of nanomaterials through effective medium theory.

Effective medium theory is introduced into a three-layer model to study the anomalous IR properties of nanostructured Pt films. A composite system is set up for the nanostructured film together with adsorbates and water around it. The anomalous IR spectral features, which exhibit a transition from enhanced (or normal) IR absorption to Fano-type bipolar line shape and, finally, to enhanced anomalous IR absorption (the abnormal infrared effects) along with the change in structure and size of nanomaterials, as observed through experiments for CO molecule adsorption, are elucidated by an increase in the volume fraction of metal in the composite system and the effective thickness of the composite system. The theoretical simulation results illustrate that the spectral line shape of IR absorption depends strongly on the volume fraction of metal, while the intensity of the IR band is directly proportional to the effective thickness. This study has revealed, through a physical optical aspect of interaction of CO molecules with nanostructured metal films, one of the possible origins of anomalous IR properties and has shed light on interpreting the peculiar properties of nanomaterials.