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To understand the potential role of microglia in synaptic pruning following status epilepticus (SE), we examined the time course of expression of Iba-1, and immune and neuroinflammatory regulators, including CD86, CD206, and CX3CR1, and TLR4/NF-κB after SE induced by pilocarpine in rats. Behavioral tests, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining, immunohistochemical staining, Western blotting, PCR, and fluorescence double staining assessments were performed. The expression of Iba-1 protein was lowest in the control group, and peaked after 2 days (p < 0.001). CD86 and CD206 mRNA levels increased gradually in the microglia of the epilepsy group after 12 hours, 1 day, 2 days, and 3 days; peak expression was on the second day. The expression of the chemokine receptor CX3CR1 in microglia increased to varying degrees after SE, and expression of the presynaptic protein synapsin decreased. The expression of TLR4/NF-κB in microglia positively correlated with Iba-1 protein expression. These findings indicate that the TLR4/NF-κB signaling pathway may be involved in the activation and polarization of microglia in epilepsy and in excess synaptic pruning, which could lead to an increase in brain injury.

We investigate the refined Carleson’s problem of the free Ostrovsky equation {ut+∂x3u+∂x−1u=0,u(x,0)=f(x),where (x, t) ∈ ℝ ×ℝ and f∈ Hs(ℝ). We illustrate the Hausdorff dimension of the divergence set for the Ostrovsky equation α1,U(s)=1−2s,14≤s≤12.

Immature granulocytes (IGs) have significance for the diagnosis of myeloid neoplasms (MNs). The current study aims to use a hematology analyzer to evaluate the accuracy of IG parameters in MNs. Blood specimens from 388 patients with MN, 524 with non-hematological neoplasms (non-HNs), including 109 patients with inflammation and 68 undergoing G-CSF administration, and 500 healthy control subjects were analyzed. IG parameters was assayed by Sysmex XN-9000 (XN) and compared with manual assessments. A high level of agreement between IG% derived from XN and manual measurements for MN patients (r= 0.828, p< 0.0001) was revealed but only a moderate correlation for acute myeloid leukemia patients (AML; r= 0.597; p< 0.0001). Bland–Altman bias analysis was conducted, and the results showed that differences in IG% from XN and manual analysis for MN patients were considered clinically insignificant. ROC analysis demonstrated a good performance of IG# (AUC = 0.842) and IG% (AUC = 0.885) assessed by XN for MN patients with cut-off values of 0.200 × 109/L and 1.95%, respectively. IG parameters from Sysmex XN analyzer are helpful for screening of MNs even though granulocyte morphological abnormalities may interfere with IG parameter accuracy.

The stabilization of the metastable tetragonal phase of BiFeO3on the highly anisotropic ZnO(11-20) surface is reported. X-ray reciprocal space maps reveal that the BiFeO3layer possesses true tetragonal symmetry rather than the monoclinic MCor MAstructures. Heteroepitaxy generates strongly anisotropic misfit strains of 2.4 and −5.3% along two orthogonal ⟨110⟩ directions of tetragonal BiFeO3. Our analysis shows that such anisotropic strains are very powerful in tailoring the energy balance of competing phases, favoring the formation of tetragonal BiFeO3. Tetragonal BiFeO3can be stabilized on the ZnO template up to a critical thickness of 110 nm, much larger than that of its monoclinic counterparts. The integration of such thick tetragonal BiFeO3films with ZnO has important implications for future applications, as exemplified by the demonstration of a prototype metal/ferroelectric/semiconductor capacitor and the preparation of flexible tetragonal BiFeO3nanomembranes. Additionally, the heteroepitaxial growth was also transposed to the integration of other perovskite oxides with ZnO. Our findings not only shed new light into the strain phase diagram of BiFeO3but also open up a possible avenue toward oxide electronics.

ABSTRACTMuscle fiber is the basic unit of skeletal muscle. Muscle fiber types play a crucial role in improving meat quality. In the current study, Wistar rats were chronic injected with 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) for four weeks in order to define the 5′-AMP-activated protein kinase (AMPK) protein activity on muscle fiber composition, enzyme activity and the mRNA expression of muscle fiber type-related genes in gastrocnemius (GS) muscle. Food intake and body weight did not show a significant difference after AICAR treatment (P > .05). The AICAR treatment caused a significantly increased number and area proportion of type I muscle fiber and expression level MyHC I mRNA (P < .05), succinic dehydrogenase (SDH) and malate dehydrogenase (MDH) activities (P < .05), but decrease in the number proportion of type IIB muscle fiber and MyHC IIb and MyHC IIx mRNA level (P < .05). The Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) mRNA level (P < .05) was increased and glucose transporter 4 (GLUT-4) mRNA level tended to be higher (P = .052) in the AICAR group. These results demonstrated that chronic AICRA treatment induces oxidative muscle fiber switching, enhances oxidative enzyme activity and GLUT4 mRNA level, mediated by PGC-1α.

The nuclear hormone receptor retinoic acid receptor-related orphan C2 (RORC2, also known as RORγt) is a promising target for the treatment of autoimmune diseases. A small molecule, inverse agonist of the receptor is anticipated to reduce production of IL-17, a key proinflammatory cytokine. Through a high-throughput screening approach, we identified a molecule displaying promising binding affinity for RORC2, inhibition of IL-17 production in Th17 cells, and selectivity against the related RORA and RORB receptor isoforms. Lead optimization to improve the potency and metabolic stability of this hit focused on two key design strategies, namely, iterative optimization driven by increasing lipophilic efficiency and structure-guided conformational restriction to achieve optimal ground state energetics and maximize receptor residence time. This approach successfully identified 3-cyano-N-(3-(1-isobutyrylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide as a potent and selective RORC2 inverse agonist, demonstrating good metabolic stability, oral bioavailability, and the ability to reduce IL-17 levels and skin inflammation in a preclinical in vivo animal model upon oral administration.

PF-06651600, a newly discovered potent JAK3-selective inhibitor, is highly efficacious at inhibiting γc cytokine signaling, which is dependent on both JAK1 and JAK3. PF-06651600 allowed the comparison of JAK3-selective inhibition to pan-JAK or JAK1-selective inhibition, in relevant immune cells to a level that could not be achieved previously without such potency and selectivity. In vitro, PF-06651600 inhibits Th1 and Th17 cell differentiation and function, and in vivoit reduces disease pathology in rat adjuvant-induced arthritis as well as in mouse experimental autoimmune encephalomyelitis models. Importantly, by sparing JAK1 function, PF-06651600 selectively targets γc cytokine pathways while preserving JAK1-dependent anti-inflammatory signaling such as the IL-10 suppressive functions following LPS treatment in macrophages and the suppression of TNFα and IL-1β production in IL-27-primed macrophages. Thus, JAK3-selective inhibition differentiates from pan-JAK or JAK1 inhibition in various immune cellular responses, which could potentially translate to advantageous clinical outcomes in inflammatory and autoimmune diseases.

Layered transition metal dichalcogenides (TMDs) with rich chemistry and diverse properties are considered promising candidates for applications in nanoscale electronics and energy conversion. Among the wide range of TMDs, niobium dichalcogenides (NbS2)are ubiquitously considered to be a great promise material for hydrogen evolution reaction (HER) due to its metallic 2D feature with good conductivity. However, a few reports focus on the systematic structural optimization of NbS2nanosheets on conductive substrates by chemical vapor deposition (CVD) towards HER. Here, vertical NbS2nanoflowers are designed and constructed on carbon cloth using CVD. Systematic growth experiments are carried out to investigate the structure variation of the nanostructures. By tuning the growth temperature, the architecture with dense exposed basal planes is achieved, which exhibits highly structure-sensitive properties for HER. The results show NbS2microflowers with maximized edge and plane sites exhibited optimal catalytic performance. The growth mechanism of NbS2nanoplates on carbon cloth is further explored. These findings provide a guideline for optimization of microstructure and electrocatalytic activity for NbS2and broaden our vision for improving HER performance of novel 2D TMDs.

Ru-B/γ-Al2O3catalyst was prepared by reductant impregnation method, which was applied in the selective hydrogenation of ethyl 1H-indole-2-carboxylate for producing ethyl 2,3,3a,7a-tetrahydro-1H-indole-2-carboxylate with hydrogen as reductant. Furthermore, we discussed the influences of substrate concentration, reaction solvent, hydrogenation temperature, initial hydrogen pressure and reaction time on the catalytic performance of the as-prepared catalyst. The obtained Ru-B/γ-Al2O3catalyst showed a high-efficiency for the selective hydrogenation of ethyl 1H-indole-2-carboxylate(>99% conversion and selectivity) in i-propanol used as solvent at a concentration of 10%(mass fraction) of ethyl 1H-indole-2-carboxylate, a pressure of hydrogen of 6 MPa and a reaction temperature of 373 K.

We report the stabilization of metastable tetragonal BiFeO3epilayer on ZnO(0001) surface. X-ray reciprocal space map characterizations show that the BiFeO3film is of true tetragonal symmetry, but not the commonly observed monoclinic structure. The critical thickness of the tetragonal BiFeO3is higher than 140 nm, much larger than that reported previously. Despite the considerable lattice mismatch and symmetry mismatch, tetragonal BiFeO3can be formed on ZnO(0001) though domain matching epitaxy which is featured by anisotropic growth. We show that by taking into account the elastic energy during the initial semi-coherent growth, the tetragonal phase is lower than the thermally stable rhombohedral phase in total energy by 70 meV per formula unit. Moreover, local piezoelectric characterizations reveal a coercive field of 360 kV cm−1and a piezoelectric constant of 48 pm V−1. The integration of tetragonal BiFeO3with robust ferroelectricity on the platform of ZnO has potentials for all-oxide electronics applications.

Exploring remarkable oxygen reduction reaction (ORR) electrocatalysts for regenerative fuel cells and metal-air batteries is highly essential. Herein, a novel non-noble metal-based heterogeneous electrocatalyst with rich defects were successfully synthesized by liquid-liquid interfacial precipitation (LLIP) of fullerene (C60) and ferrotetraphenylporphyrin (FeTPP) followed by one step pyrolysis. The obtained product annealed at 700°C (C60/FeTPP-700), when employed as ORR electrocatalyst, revealed a positive half-wave potential (E1/2) of 0.877 V vs. reversible hydrogen electrode (RHE), which was superior to that of the commercial 25% Pt/C. Delightfully, the assembled Zn-air battery (ZAB) using C60/FeTPP-700 as an air-electrode catalyst exhibited a high power density of 153 mW/cm2, specific capacity of 668 mAh/g and long-term cycling stability for more than 250 h. Experimental results proved that the excellent electrocatalytic ORR activity of C60/FeTPP-700 would attribute to the synergistic effect between FeNxsites, Fe3C/Fe nanoparticles and the structure defects. This work provides a feasible and simple method to prepare non-noble metal-based ORR electrocatalysts for the application of energy storage and conversion.

A unique model of hypertension developed in our laboratory shows that neonatal degeneration of capsaicin-sensitive sensory nerves renders a rat responsive to salt load with a significant rise in blood pressure. Considering that capsaicin impairs the micturition reflex, increased retention of urine in the bladder of capsaicin-treated rats may lead to nephropathy and therefore to an increase in blood pressure. The present study was designed to test the hypothesis that abnormalities in renal function and blood pressure in this model are independent of urine retention, and are reversible when a high-salt diet is withdrawn.

AbstractAcidichromism of four photochromic spirooxazine compounds (SP) were investigated systematically. When hydroxyl group is introduced on the naphtho ring of spirooxazine, the spirooxazine compounds are found to have acidichromic properties in both acidic and basic solutions. Substituent effect on the absorption maximum of acidichromic products has been discussed. A comprehensive discussion of acidichromic, photochromic and thermochromic processes is included.

The progression of muscular weakness of patients suffering from muscular dystrophies directly correlates with the progressive loss of myofibers, accompanied by fibrosis. Since transforming growth factor β1 (TGF-β1) promotes tissue fibrosis, we measured the plasma TGF-β1 level in patients with various muscular dystrophies in order to determine whether the level is elevated in patients with muscular dystrophy and if the level reflects the severity of tissue fibrosis. The plasma TGF-β1 level was significantly elevated in patients with Duchenne muscular dystrophy and congenital muscular dystrophy (CMD), but not in those with Becker muscular dystrophy. Growth factors related to muscle fiber regeneration and fibrosis might be a key factor in the progression of muscular dystrophy and could be a target for therapeutic studies.