SEP-363856 exerts neuroprotection through the PI3K/AKT/GSK-3ß signaling pathway in a dual-hit neurodevelopmental model of schizophrenia-like mice.

Schizophrenia (SZ) is a serious, destructive neurodevelopmental disorder. Antipsychotic medications are the primary therapy approach for this illness, but it's important to pay attention to the adverse effects as well. Clinical studies for SZ are currently in phase ΙΙΙ for SEP-363856 (SEP-856)-a new antipsychotic that doesn't work on dopamine D2 receptors. However, the underlying action mechanism of SEP-856 remains unknown. This study aimed to evaluate the impact and underlying mechanisms of SEP-856 on SZ-like behavior in a perinatal MK-801 treatment combined with social isolation from the weaning to adulthood model (MK-SI). First, we created an animal model that resembles SZ that combines the perinatal MK-801 with social isolation from weaning to adulthood. Then, different classical behavioral tests were used to evaluate the antipsychotic properties of SEP-856. The levels of proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-1ß), apoptosis-related genes (Bax and Bcl-2), and synaptic plasticity-related genes (brain-derived neurotrophic factor [BDNF] and PSD-95) in the hippocampus were analyzed by quantitative real-time PCR. Hematoxylin and eosin staining were used to observe the morphology of neurons in the hippocampal DG subregions. Western blot was performed to detect the protein expression levels of BDNF, PSD-95, Bax, Bcl-2, PI3K, p-PI3K, AKT, p-AKT, GSK-3ß, p-GSK-3ß in the hippocampus. MK-SI neurodevelopmental disease model studies have shown that compared with sham group, MK-SI group exhibit higher levels of autonomic activity, stereotyped behaviors, withdrawal from social interactions, dysregulated sensorimotor gating, and impaired recognition and spatial memory. These findings imply that the MK-SI model can mimic symptoms similar to those of SZ. Compared with the MK-SI model, high doses of SEP-856 all significantly reduced increased activity, improved social interaction, reduced stereotyping behavior, reversed sensorimotor gating dysregulation, and improved recognition memory and spatial memory impairment in MK-SI mice. In addition, SEP-856 can reduce the release of proinflammatory factors in the MK-SI model, promote the expression of BDNF and PSD-95 in the hippocampus, correct the Bax/Bcl-2 imbalance, turn on the PI3K/AKT/GSK-3ß signaling pathway, and ultimately help the MK-SI mice's behavioral abnormalities. SEP-856 may play an antipsychotic role in MK-SI "dual-hit" model-induced SZ-like behavior mice by promoting synaptic plasticity recovery, decreasing death of hippocampal neurons, lowering the production of pro-inflammatory substances in the hippocampal region, and subsequently initiating the PI3K/AKT/GSK-3ß signaling cascade.

Effect of Boron Doping on the Interlayer Spacing of Graphite.

Boron-doped graphite was prepared by the heat treatment of coke using B4C powder as a graphitization catalyst to investigate the effects of the substitutional boron atoms on the interlayer spacing of graphite. Boron atoms can be successfully incorporated into the lattice of graphite by heat treatment, resulting in a reduction in the interlayer spacing of graphite to a value close to that of ideal graphite (0.3354 nm). With an increase in the catalyst mass ratio, the content of substituted boron in the samples increased significantly, causing a decrease in the interlayer spacing of the boron-doped graphite. Density functional theory calculations suggested that the effects of the substitutional boron atoms on the interlayer spacing of the graphite may be attributed to the transfer of Π electrons between layers, the increase in the electrostatic surface potential of the carbon layer due to the electron-deficient nature of boron atoms, and Poisson contraction along the c-axis.

Enhanced Thermoelectric Properties of Te Doped Polycrystalline Sn0.94Pb0.01Se.

Thermoelectric materials can directly convert heat and electricity, which is a kind of promising energy material. In view of cost and mechanical properties, polycrystalline SnSe material with high zT value is greatly desired. In this study, polycrystalline Sn0.94Pb0.01Se1-xTex samples were prepared by the vacuum melting-hot pressing sintering method. Sn vacancies, Pb and Te atoms were simultaneously introduced into the polycrystalline SnSe. The power factor of Sn0.94Pb0.01Se1-xTex samples was decreased, which could be attributed to the generation of n-type semiconductor SnSe2. In addition, the phonons were strongly scattered by point defects and dislocations, which led to the decrease of thermal conductivity-from 0.43 Wm-1K-1 to 0.29 Wm-1K-1 at 750 K. Finally, the polycrystalline Sn0.94Pb0.01Se0.96Te0.04 sample achieved the maximum zT value of 0.60 at 750 K.

Enhanced Thermoelectric Performance of Cu2Se via Nanostructure and Compositional Gradient.

Forming co-alloying solid solutions has long been considered as an effective strategy for improving thermoelectric performance. Herein, the dense Cu2-x(MnFeNi)xSe (x = 0-0.09) with intrinsically low thermal conductivity was prepared by a melting-ball milling-hot pressing process. The influences of nanostructure and compositional gradient on the microstructure and thermoelectric properties of Cu2Se were evaluated. It was found that the thermal conductivity decreased from 1.54 Wm-1K-1 to 0.64 Wm-1K-1 at 300 K via the phonon scattering mechanisms caused by atomic disorder and nano defects. The maximum zT value for the Cu1.91(MnFeNi)0.09Se sample was 1.08 at 750 K, which was about 27% higher than that of a pristine sample.

Revealing molecular conformation-induced stress at embedded interfaces of organic optoelectronic devices by sum frequency generation spectroscopy.

Interface stresses are pervasive and critical in conventional optoelectronic devices and generally lead to many failures and reliability problems. However, detection of the interface stress embedded in organic optoelectronic devices is a long-standing problem, which causes the unknown relationship between interface stress and organic device stability (one key and unsettled issue for practical applications). In this study, a kind of previously unknown molecular conformation-induced stress is revealed at the organic embedded interface through sum frequency generation (SFG) spectroscopy technique. This stress can be greater than 10 kcal/mol per nm2 and is sufficient to induce molecular disorder in the organic semiconductor layer (with energy below 8 kcal/mol per nm2), finally causing instability of the organic transistor. This study not only reveals interface stress in organic devices but also correlates instability of organic devices with the interface stress for the first time, offering an effective solution for improving device stability.

Fe3+-codoped ultra-small NaGdF4:Nd3+ nanophosphors: enhanced near-infrared luminescence, reduced particle size and bioimaging applications.

Small-sized lanthanide-doped nanoparticles (NPs) exhibiting superior near-infrared (NIR) luminescence properties are highly desired for bioimaging applications. Herein, Fe3+ ions are codoped in NaGdF4:Nd3+ nanocrystals via a simple coprecipitation method, which can simultaneously reduce the particle size and enhance the downconverting NIR luminescence of the NPs. The NIR luminescence intensity reaches the maximum for the obtained sub-5 nm NPs when the doping concentration of Fe3+ is tuned to 20 mol%, which is ∼1.7 times higher than that of the pristine 8.7 nm NPs without Fe3+ doping. After being modified with targeting molecules, the ultra-small NaGdF4:Nd3+,Fe3+ NPs were successfully applied as luminescent probes for targeted NIR imaging of tumors in biological tissues. Moreover, they also show great potential as a high contrast agent for T2-weighted MRI imaging.

Facile and Scalable Fabrication of CuO Nanoflakes with Excellent Catalytic Properties.

Well dispersed CuO nanoflakes were successfully achieved via a fast and self-heating route. The physical properties of the as-prepared products were analyzed by X-ray powder diffraction (XRD), field emission scanning electron microscopy (FESEM), nitrogen adsorption-desorption measurements, transmission electron microscopy (TEM) and selected area electron diffraction (SAED). Meanwhile, the catalytic activity and the catalytic advantage of CuO nanostructures are discussed with the help of first-order kinetics investigation for methylene blue degradation. It is found that self-heating in the reaction mixture and formation of cellular CuO network fully filled with oxygen bubble are mainly responsible for synthesis of CuO nanoflakes. Meanwhile, the as-obtained CuO nanoflakes possessed high specific surface area and exhibited high catalytic characteristics with wet hydrogen peroxide oxidation in methylene blue solution. The present work is likely to be favorable for taking full advantage of the catalytic activity of CuO nanostructures with high specific surface area for the wet hydrogen peroxide oxidation of dyes.

Neodymium-doped NaHoF4 nanoparticles as near-infrared luminescent/T2-weighted MR dual-modal imaging agents in vivo.

The achievement of efficient near-infrared (NIR) luminescence of lanthanide ions in a paramagnetic nanoparticle (NP) host is highly desirable to optimize the performance of multimodal bioprobes. Herein, we present a facile coprecipitation method to prepare highly uniform NaHoF4:Nd3+ nanoplates. Upon NIR excitation at 785 nm, efficient NIR luminescence of Nd3+ can be obtained from the paramagnetic NaHoF4 hosts. More interestingly, due to energy transfer from the excited state of Nd3+ to the adjacent Ho3+, NIR emission at around 1200 nm from Ho3+ ions is also observed. The r2 value of NaHoF4:Nd3+ NPs reaches 143.7 s-1 mM-1 at a high magnetic field of 11.7 T. By modifying with hydrophilic alpha-cyclodextrin, the NaHoF4:Nd3+ NPs were further successfully applied for the NIR luminescent/T2-weighted MR dual-modal in vivo imaging of nude mice, high contrast NIR imaging of the liver and T2-weighted MR imaging of stem cells in the mouse brain using the NaHoF4:Nd3+ NPs as multimodal bioprobes.

915 nm Light-Triggered Photodynamic Therapy and MR/CT Dual-Modal Imaging of Tumor Based on the Nonstoichiometric Na0.52 YbF3.52 :Er Upconversion Nanoprobes.

Lanthanide (Ln(3+) )-doped upconversion nanoparticles (UCNPs) as a new generation of multimodal bioprobes have attracted great interest for theranostic purpose. Herein, red emitting nonstoichiometric Na0.52 YbF3.52 :Er UCNPs of high luminescence intensity and color purity are synthesized via a facile solvothermal method. The red UC emission from the present nanophosphors is three times more intense than the well-known green emission from the ≈30 nm sized hexagonal-phase NaYF4 :Yb,Er UCNPs. By utilizing Na0.52 YbF3.52 :Er@SrF2 UCNPs as multifunctional nanoplatforms, highly efficient in vitro and in vivo 915 nm light-triggered photodynamic therapies are realized for the first time, with dramatically diminished overheating yet similar therapeutic effects in comparison to those triggered by 980 nm light. Moreover, by virtue of the high transverse relaxivity (r 2 ) and the strong X-ray attenuation ability of Yb(3+) ions, these UCNPs also demonstrate good performances as contrast agents for high contrast magnetic resonance and X-ray computed tomography dual-modal imaging. Our research shows the great potential of the red emitting Na0.52 YbF3.52 :Er UCNPs for multimodal imaging-guided photodynamic therapy of tumors.

Organized Molecular Interface-Induced Noncrystallizable Polymer Ultrathin Nanosheets with Ordered Chain Alignment.

The orientation and state of organization of polymer chains play significant roles in determining the final properties and functions of these materials. Unlike most semicrystalline polymers, which have an inherent driving force toward crystallization, the means to control chain packing in noncrystallizable polymers is still restricted and remains a challenge. We report herein a 2D soft template-directed fabrication for ultrathin polyacrylamide nanosheets with a thickness as low as 3.5 nm and large dimensions (>20 µm). More importantly, the polymer chains in the nanosheets produced are well aligned with a clear interchain spacing. The formation of polymer nanosheets with ordered chain alignment was performed in a special solution containing a periodic sandwich structure of lamellar bilayer membranes and water layers that are hundreds of nanometers thick. It functions as a 2D orientation template to align the monomers in an orderly manner along the in-plane direction of the bimolecular membrane via hydrogen bonding.

Conformation of Capping Ligands on Nanoplates: Facet-Edge-Induced Disorder and Self-Assembly-Related Ordering Revealed by Sum Frequency Generation Spectroscopy.

Surface-curvature-amplified conformational disorder in alkyl capping ligands has been observed previously when the nanoparticle radii approach the ligand length. Herein, sum frequency generation studies on oleic-acid-capped nanoplates show that even on faceted surfaces with dimensions tens of times greater than the ligand length a significant proportion of gauche defects exist in the capping layer. The molecular disorder on the nanosized facets is attributed to a facet-edge effect, which is diminished when increasing the facet size or assembling the nanofacets side to side. This feature is further explored to probe the self-assembly dynamics of nanoplates.

Rational design of a thermalresponsive-polymer-switchable FRET system for enhancing the temperature sensitivity of upconversion nanophosphors.

Here we propose a thermoresponsive polymer PNIPAM modulated fluorescence resonance energy transfer (FRET) system to enhance the temperature sensitivity of upconversion nanophosphors (UCNPs). By utilizing red/near-infrared dual emitting NaLuF4:Mn(2+),Ln(3+) (Ln(3+) = Yb(3+), Er(3+), Tm(3+)) UCNPs as the energy donor and Au nanoparticles as the acceptor, the temperature resolution of the UCNPs is significantly increased from 3.1 °C to 0.9 °C in the physiological temperature range. Conjugating the UCNPs and acceptors into discrete nanocomposites in our samples facilitates reversible regulation of the emission intensity of UCNPs, which thus would extend their application range in biosensing, especially for probing the dynamic changes of local micro-environments in biological tissues. As there are a broad variety of stimuli to which smart polymers can reversibly respond, our experiments are also extendable to various external conditions in local micro-environments, such as pH values, metal ions, glucose, and tissue-specific enzymes.

Association between IL-6-174G/C polymorphism and risk of multiple sclerosis: a meta-analysis.

OBJECTIVE: Interleukin-6 (IL-6) is a pleiotropic cytokine and important mediator of many inflammatory processes, which might affect susceptibility to multiple sclerosis (MS). The aim of this study was to assess the effect of IL-6-174G/C polymorphism on the risk of MS using a meta-analysis. MATERIALS AND METHODS: The Pubmed, ISI Web of Science, Wanfang, VIP, and China National Knowledge Infrastructure databases were screened and six studies were included in the meta-analysis. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CI) were calculated to evaluate the association between the IL-6-174G/C polymorphism and risk of MS. RESULTS: No significant association between the IL-6-174G/C polymorphism and risk of MS was observed in overall analyses. With stratification according to ethnicity, we found that carriers with the IL-6-174CC genotype had a 1.87-fold increased risk for the development of MS in Asians (recessive model: OR=1.87, 95% CI, 1.08-3.24), but not in Caucasians. CONCLUSION: This meta-analysis provides evidence that the IL-6-174G/C polymorphism may be a risk factor for the development of MS in Asians. Further association studies with a larger sample size are required to confirm the result in different populations.