Phoenixin 14 inhibits ischemia/reperfusion-induced cytotoxicity in microglia.

The process of ischemia/reperfusion (IR) in ischemic stroke often leads to significant cell death and permanent neuronal damage. Safe and effective treatments are urgently needed to mitigate the damage caused by IR injury. The naturally occurring pleiotropic peptide phoenixin 14 (PNX-14) has recently come to light as a potential treatment for IR injury. In the present study, we examined the effects of PNX-14 on several key processes involved in ischemic injury, such as pro-inflammatory cytokine expression, oxidative stress, and the related cascade mediated through the toll-like receptor 4 (TLR4) pathway, using BV2 microglia exposed to oxygen-glucose deprivation and reoxygenation (OGD/R). Our results demonstrate an acute ability of PNX-14 to regulate the expression levels of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). PNX-14 also prevented oxidative stress by reducing the generation of reactive oxygen species (ROS) and increasing the level of the antioxidant glutathione (GSH). Importantly, PNX-14 inhibited high-mobility group box 1 (HMGB1)/TLR4/myeloid differentiation primary response 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway, by inhibiting the activation of TLR4 and preventing the nuclear translocation of p65 protein. We further confirmed the cerebroprotective effects of PNX-14 in an MCAO rat model, which resulted in reduced infarct volume and decreased microglia activation. Together, the results of this study implicate a possible protective role of PNX-14 against various aspects of IR injury in vitro.

Plasma Levels of Cyclooxygenase-2 (COX-2) and Visfatin During Different Stages and Different Subtypes of Migraine Headaches.

BACKGROUND The aim of this study was to determine the plasma levels of cyclooxygenase-2 (COX-2) and visfatin in different stages and different subtypes of migraine headaches compared to a control group to elucidate the pathological mechanisms involved. MATERIAL AND METHODS We recruited a case-control cohort of 182 adult migraine patients and 80 age-matched and gender-matched healthy controls. The migraine patients were divided into two groups: the headache-attack-period group (Group A, n=77) and the headache-free-period group (Group B, n=105). The two groups were further divided into subgroups according to whether they had aura symptoms. Solid phase double antibody sandwich enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma levels of COX-2 and visfatin. Statistical analysis was performed using SPSS 17.0. RESULTS The plasma levels of COX-2 and visfatin in the headache-attack-period group were significantly higher than in the headache-free-period group and the control group; there were no significant differences between the headache-free group and the control group. There were no significant differences in plasma levels of COX-2 and visfatin between the subgroups: headache-attack-period with aura subgroup and the headache-attack-period without aura sub group. CONCLUSIONS COX-2 and visfatin participated in the pathogenesis of migraine headaches. The presence of aura had no effect on the serum levels of COX-2 and visfatin.

Correlating structure and electronic band-edge properties in organolead halide perovskites nanoparticles.

After having emerged as primary contenders in the race for highly efficient optoelectronics materials, organolead halide perovskites (OHLP) are now being investigated in the nanoscale regime as promising building blocks with unique properties. For example, unlike their bulk counterpart, quantum dots of OHLP are brightly luminescent, owing to large exciton binding energies that cannot be rationalized solely on the basis of quantum confinement. Here, we establish the direct correlation between the structure and the electronic band-edge properties of CH3NH3PbBr3 nanoparticles. Complementary structural and spectroscopic measurements probing long-range and local order reveal that lattice strain influences the nature of the valence band and modifies the subtle stereochemical activity of the Pb(2+) lone-pair. More generally, this work demonstrates that the stereochemical activity of the lone-pair at the metal site is a specific physicochemical parameter coupled to composition, size and strain, which can be employed to engineer novel functionalities in OHLP nanomaterials.

Characterization of transcriptional profiling of Kupffer cells during liver regeneration in rats.

KCs (Kupffer cells), as an important hepatic immunoregulatory cells, play a key role in LR (liver regeneration). Uncovering the transcriptional profiling of KCs after PH (partial hepatectomy) would likely clarify its implication in LR. Here, we isolated KCs by methods of Percoll density gradient centrifugation and immunomagnetic beads. Transcriptional profiles of KCs were monitored up to 168 h post-PH using microarray. By comparing the expression profile of KCs at 2-168 h post-PH with that of the control and applying the statistical and bioinformatics criteria, we found 1407 known and 927 unknown genes related to LR. K-means clustering analysis grouped these 1407 genes into robust 14 time-course clusters representing distinct patterns of regulation. Based on gene-set enrichment analysis, genes encoding products involved in cytokine signalling, inflammatory response and cell chaemotaxis were highly enriched in the cluster characterized by gradual up-regulation and then return; genes in defence response and immune response were enriched in clusters 'the general down-regulation during LR'; genes in fatty acid synthesis and sterol metabolism were preferentially distributed in the cluster 'gradual increase'; whereas genes in the categories 'lipid catabolism' and 'glycolysis' were enriched in cluster 'decrease at two intervals'. According to the above analysis, KCs were seemingly sensitive to operative stimulus; immune defence and detoxification function of KCs obviously dropped post-operatively; fatty acid synthesis were enhanced, whereas lipid catabolism and glycolysis were reduced after PH. This study provides a detailed in vivo gene expression profile of KCs, providing a framework to better understand the molecular mechanisms underlying the regeneration process at cellular level.

Impact of N, O Heteroatoms in Asphaltene on Adsorption of Vanadyl/Nickel Etioporphyrin.

The interaction between functionalized graphene and metal porphyrins was studied for a better understanding of the influence of the N and O heteroatoms in asphaltene on demetallization efficiency during the solvent deasphalting process. The theoretical simulation indicated a strong inhibitory effect of the aminated/carboxylated side group for chemical adsorption of metal porphyrins. The differences of adsorption behavior for graphene, aminated graphene, and Canadian oil sands bitumen vacuum tower bottom asphaltene (VTB-asp) were also analyzed. It was found that the introduction of aminated side groups to the graphene not only compromised the electron delocalization capacity of the polyaromatic nuclei hydrocarbon skeleton of graphene but also caused a steric hindrance effect on the internal diffusion of metal porphyrins, leading to decreased adsorption active sites and internal diffusion rate, respectively. It was also found that metal porphyrins can be barely adsorbed on carboxylated graphene at 25 °C.

Analysis of time-course gene expression profiles of sinusoidal endothelial cells during liver regeneration in rats.

Liver regeneration (LR) after partial hepatectomy (PH) requires the coordinate contribution of different cell types. Liver sinusoidal endothelial cells (LSECs), representing the largest population of nonparenchymal cells, are proven to be crucial in LR. However, the details about their implications in regeneration are not still clear. In this study, percoll density centrifugation and immunomagentic bead methods were used to isolate LSECs with high purity and yield; global transcriptional profiles of LSECs during the regeneration were investigated by microarray. 1,629 genes were identified to be LR-related. Among them, there were 833 known genes whose expression patterns were clustered into eight classes. Gene function enrichment analysis showed that genes involved in the major LSEC functions, i.e., coagulation, phagocytosis, and transport, were highly enriched in cluster characterized by rapid induction and gradual return, suggesting the quick reestablishment of LSEC function after PH. Genes in immunity/inflammation and defense response were enriched in clusters exhibiting transient downregulation and quick recovery, possibly being associated with suppression of immunity/inflammation pathway in LSECs at early phase. Genes in glycogen synthesis and glycolysis were enriched in the clusters marked by "significant increase and gradual return" and "slight increase and then downregulation", implying an enhanced carbohydrate metabolism at early phase; detoxification-related genes were markedly distributed in the cluster with feature of rapid increase and then reduction, which was helpful in eliminating waste substance. Taken together, the measurement of gene expression profiling of LSECs and expression pattern analysis of functionally categorized genes gave insight into the mechanism of action of this cell on LR.

Genome-wide analysis of gene expression in dendritic cells from rat regenerating liver after partial hepatectomy.

Dendritic cells (DCs) play a pivotal role in orchestrating immune response occurring in liver regeneration (LR). However, there are few details about relationship between DCs and LR at the molecular level. In this study, we firstly obtained high-purity DCs by the combination of Percoll density gradient centrifugation and immunomagentic bead sorting, then measured genome-wide gene expression in DCs from rat regenerating liver after partial hepatectomy (PH) using rat genome 230 2·0 microarray composed of 25,020 genes, and verified the reliability of microarray data with RT-PCR method. Among 25,020 genes present on the array, 1621 known genes and 1307 unknown genes, totally 2928 genes, were identified to be LR-related. H-clustering analysis showed that 2928 genes were grouped into three expression patterns: up-regulation, down-regulation and complex changes in expression. And 1621 known genes were functionally grouped into at least 23 biological categories. When expression patterns were combined with gene functions, as a whole, the genes involved in immune/defence response, inflammatory response and secretion of active substance in DCs were highly enriched in down-regulated pattern. DCs exhibited the reduced immune/defence and inflammatory response, and the suppressed secretion capacity of active substances after PH. A further analysis of genes expressed in the phase-dependent manner during LR suggested the rapid induction of genes encoding some transcription factors and cytokines in DCs at immediate-early phase, the unobvious enhancement of metabolic process, immunity and inflammation at proliferation phase, while the impairment of detoxification, immunity and inflammation at terminal phase.

Transcriptome analysis of hepatocytes after partial hepatectomy in rats.

After partial hepatectomy (PH), the recovery of liver mass is mainly mediated by proliferation and enlargement of hepatocytes. Therefore, measuring the transcriptional profiling of hepatocytes after PH will be helpful in exploring the mechanism of liver regeneration (LR). Firstly, hepatocytes were isolated from rat regenerating liver at different time points following PH, and then global gene expression analysis of hepatocytes was performed using Rat Genome 230 2.0 Array. The results demonstrated that 1,417 genes in the array (including 767 known genes) were identified to be LR-related. Clustering analysis demonstrated that 767 known genes fell into six classes with distinct expression kinetics. When gene expression patterns were combined with gene functions, genes involved in acute-phase response and defense response were rapidly elevated in early phases; those in cell proliferation and DNA replication were significantly up-expressed in middle phase; a growing number of cell adhesion-involved genes were up-regulated as regeneration progressed; those in amino acid and lipid metabolism showed persistent down-regulation during LR. Based on the above analyses, it was suggested that hepatocyte defense mechanism was quickly triggered after PH; cell proliferation became active in middle phase; cell adhesion was strengthened in late phase; amino acid and lipid metabolism were attenuated during LR. Additionally, comparative analysis between transcriptional profiling of hepatocytes and regenerating liver indicated a major contribution of hepatocytes to LR.

[Transcriptome atlas of serine family amino acid metabolism-related genes in eight rat regenerating liver cell types.].

To explore the transcription profiles of serine family amino acid metabolism-related genes in eight liver cell types during rat liver regeneration (LR), eight types of rat regenerating liver cells were isolated using the combination of percoll density gradient centrifugation and immunomagnetic bead methods. Then, the expression profiles of the genes associated with metabolism of serine family amino acid in rat liver regeneration were detected by Rat Genome 230 2.0 Array. The expression patterns of these genes were analyzed through the software of Cluster and Treeview. The activities of serine family amino acid metabolism were analyzed by the methods of bioinformatics and systems biology. The results showed that 27 genes were significantly expressed. Among them, the numbers of genes showing significant expression changes in hepatocytes, biliary epithelial cells, oval cells, hepatic stellate cells, sinusoidal endothelial cells, Kupffer cells, pit cells and dendritic cells were 13, 16, 11, 14, 13, 11, 12, and 14, respectively. The numbers of up-, down-, and up-/down-regulated genes in corresponding cells were 7, 6, and 0; 2, 10, and 4; 2, 8, and 1; 8, 3, and 3; 6, 5, and 2; 4, 6, and 1; 2, 10, and 0; and 6, 6, and 2. Overall, the genes in the eight types of cells were mostly down-regulated during liver regeneration, but most LR-related genes in hepatic stellate cells and sinusoidal endothelial cells were up-regulated in priming phase. It is suggested that biosynthesis of serine family amino acid was enhanced in hepatocytes, hepatic stellate cells, sinusoidal endothelial cells and Kupffer cells in the priming phase. The catabolism of them was enhanced in hepatocytes, biliary epithelial cells, pit cells and dendritic cells in progressive phase.

Drastic difference between hole and electron injection through the gradient shell of CdxSeyZn1-xS1-y quantum dots.

Ultrafast fluorescence spectroscopy was used to investigate the hole injection in CdxSeyZn1-xS1-y gradient core-shell quantum dot (CSQD) sensitized p-type NiO photocathodes. A series of CSQDs with a wide range of shell thicknesses was studied. Complementary photoelectrochemical cell measurements were carried out to confirm that the hole injection from the active core through the gradient shell to NiO takes place. The hole injection from the valence band of the QDs to NiO depends much less on the shell thickness when compared to the corresponding electron injection to n-type semiconductor (ZnO). We simulate the charge carrier tunneling through the potential barrier due to the gradient shell by numerically solving the Schrödinger equation. The details of the band alignment determining the potential barrier are obtained from X-ray spectroscopy measurements. The observed drastic differences between the hole and electron injection are consistent with a model where the hole effective mass decreases, while the gradient shell thickness increases.

Direct Experimental Evidence for Photoinduced Strong-Coupling Polarons in Organolead Halide Perovskite Nanoparticles.

Echoing the roaring success of their bulk counterparts, nano-objects built from organolead halide perovskites (OLHP) present bright prospects for surpassing the performances of their conventional organic and inorganic analogues in photodriven technologies. Unraveling the photoinduced charge dynamics is essential for optimizing the optoelectronic functionalities. However, mapping the carrier-lattice interactions remains challenging, owing to their manifestations on multiple length scales and time scales. By correlating ultrafast time-resolved optical and X-ray absorption measurements, this work reveals the photoinduced formation of strong-coupling polarons in CH3NH3PbBr3 nanoparticles. Such polarons originate from the self-trapping of electrons in the Coulombic field caused by the displaced inorganic nuclei and the oriented organic cations. The transient structural change detected at the Pb L3 X-ray absorption edge is well-captured by a distortion with average bond elongation in the [PbBr6]2- motif. General implications for designing novel OLHP nanomaterials targeting the active utilization of these quasi-particles are outlined.

Exciton Binding Energy and the Nature of Emissive States in Organometal Halide Perovskites.

Characteristics of nanoscale materials are often different from the corresponding bulk properties providing new, sometimes unexpected, opportunities for applications. Here we investigate the properties of 8 nm colloidal nanoparticles of MAPbBr3 perovskites and contrast them to the ones of large microcrystallites representing a bulk. X-ray spectroscopies provide an exciton binding energy of 0.32 ± 0.10 eV in the nanoparticles. This is 5 times higher than the value of bulk crystals (0.084 ± 0.010 eV), and readily explains the high fluorescence quantum yield in nanoparticles. In the bulk, at high excitation concentrations, the fluorescence intensity has quadratic behavior following the Saha-Langmuir model due to the nongeminate recombination of charges forming the emissive exciton states. In the nanoparticles, a linear dependence is observed since the excitation concentration per particle is significantly less than one. Even the bulk shows linear emission intensity dependence at lower excitation concentrations. In this case, the average excitation spacing becomes larger than the carrier diffusion length suppressing the nongeminate recombination. From these considerations we obtain the charge carrier diffusion length in MAPbBr3 of 100 nm.

Sandwiched confinement of quantum dots in graphene matrix for efficient electron transfer and photocurrent production.

Quantum dots (QDs) and graphene are both promising materials for the development of new-generation optoelectronic devices. Towards this end, synergic assembly of these two building blocks is a key step but remains a challenge. Here, we show a one-step strategy for organizing QDs in a graphene matrix via interfacial self-assembly, leading to the formation of sandwiched hybrid QD-graphene nanofilms. We have explored structural features, electron transfer kinetics and photocurrent generation capacity of such hybrid nanofilms using a wide variety of advanced techniques. Graphene nanosheets interlink QDs and significantly improve electronic coupling, resulting in fast electron transfer from photoexcited QDs to graphene with a rate constant of 1.3 × 10(9) s(-1). Efficient electron transfer dramatically enhances photocurrent generation in a liquid-junction QD-sensitized solar cell where the hybrid nanofilm acts as a photoanode. We thereby demonstrate a cost-effective method to construct large-area QD-graphene hybrid nanofilms with straightforward scale-up potential for optoelectronic applications.

Thermally Activated Exciton Dissociation and Recombination Control the Carrier Dynamics in Organometal Halide Perovskite.

Solar cells based on organometal halide perovskites have seen rapidly increasing efficiencies, now exceeding 15%. Despite this progress, there is still limited knowledge on the fundamental photophysics. Here we use microwave photoconductance and photoluminescence measurements to investigate the temperature dependence of the carrier generation, mobility, and recombination in (CH3NH3)PbI3. At temperatures maintaining the tetragonal crystal phase of the perovskite, we find an exciton binding energy of about 32 meV, leading to a temperature-dependent yield of highly mobile (6.2 cm(2)/(V s) at 300 K) charge carriers. At higher laser intensities, second-order recombination with a rate constant of γ = 13 × 10(-10) cm(3) s(-1) becomes apparent. Reducing the temperature results in increasing charge carrier mobilities following a T(-1.6) dependence, which we attribute to a reduction in phonon scattering (Σµ = 16 cm(2)/(V s) at 165 K). Despite the fact that Σµ increases, γ diminishes with a factor six, implying that charge recombination in (CH3NH3)PbI3 is temperature activated. The results underline the importance of the perovskite crystal structure, the exciton binding energy, and the activation energy for recombination as key factors in optimizing new perovskite materials.

Genome-wide expression profiling of hepatic oval cells after partial hepatectomy in rats.

To examine the changes of biological activities in hepatic oval cells (HOCs) elicited by 70% partial hepatectomy (PH) and understand the relationship between this cell and liver regeneration (LR), this study isolated and obtained the high purity HOCs (≥ 95%) from rat regenerating livers, and then monitored gene expression profiling of rat hepatic oval cells following surgical operation. Results showed that there were LR-related 1059 genes. These genes were grossly classified into three groups using a fold change cut-off threshold of three-fold: up-regulation, down-regulation and up/down regulation. Analyses of gene expression patterns combined with gene functional categorization suggested that genes in the categories "nucleic acid metabolism" and "cell cycle" were dominated by up-regulated expression. Genes in the functional groups "cell metabolism" and "oxidation reduction" were significantly enriched in expression pattern characterized by down-regulation. According to above mentioned results, the synchronized induction of DNA replication and cell proliferation-involved genes suggested that the peak of oval cell proliferation might occur between 30 and 36 h post-PH. The amino acid transformation-involved genes were down-regulated at the early phase of LR, which perhaps trigger the storage of those amino acids essential for protein synthesis. Reduced oxidative-reduction activity at early phase might be related to negative influence of surgical operation on its detoxification capacity. Conclusively, the genome-wide transcriptional analysis of oval cells would contribute to our understanding of the nature of LR at cell level.

Analysis of gene expression profiles of liver stellate cells during liver regeneration in rats.

This study performed a large-scale, high-throughput analysis of transcriptional profiling of liver stellate cells (LSCs) at the cellular level to investigate changes in the biological activity of LSCs during rat liver regeneration (LR) and the relation of these changes to LR. First, a rat liver regeneration model was established by partial hepatectomy (PH). Stellate cells were isolated in high purity and yield from the regenerating rat liver by Percoll density gradient centrifugation and immunomagnetic bead sorting. The changes in gene expression of LSCs after PH were examined using a rat genome 230 2.0 array composed of 24622 genes. The results indicated that 10241 of the 24622 genes investigated on the array were differentially expressed in LSCs. Of the 10241 genes, 1563 known genes were related to LR, which were grouped into three major gene expression clusters according to three-fold cut-off threshold: the upregulated gene cluster, the down-regulated gene cluster, and the cluster composed of genes showing complex changes in expression. Additionally, the genes were grouped into those involved in transcription regulation, signal transduction, transport, cellular metabolism, inflammation and immunity by functional analysis. When gene expression profiles were combined with the results of gene functional analysis, most of the genes involved in cytokine secretion and retinol metabolism in LSCs were significantly enriched in the cluster characterized by decreased expression, whereas genes involved in lipid metabolism were mostly enriched in the cluster showing increased expression. Based on further analysis of genes expressed in a phase-dependent manner during LR, it was suggested that lipid metabolism in LSCs was enhanced in the whole regeneration process, and that immune response and cytokine secretion were impaired during all three regenerative phases.