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Epigallocatechin-3-gallate (EGCG) is the most biologically active catechin of green tea. Tacrolimus (TAC) and cyclosporine A (CsA) are immunosuppressive agents commonly used in clinical organ transplantation. The present study investigated the effect of EGCG on the pharmacokinetics of TAC and CsA in rats and its underlying mechanisms.Either TAC or CsA was administered to rats intravenously or orally with or without concomitant EGCG. Polymerase Chain Reaction and Western Blot were used to determine the effect of EGCG on drug-metabolizing enzymes (DMEs), drug transporters (DTs) and nuclear receptors (NRs).The CThese results revealed consumption of high dose EGCG may cause a significant alteration in pharmacokinetics of TAC and distribution/elimination profiles of CsA through the regulation of DMEs, DTs and NRs.

Fluralaner, a systemic pesticide, was originally registered with the US Food and Drug Administration in 2014 under the trade name Bravecto for flea treatment for pets. As a GABA antagonist, the footprint of fluralaner has expended beyond medical and veterinary pests in recent years. In this study, we examined the acute toxicity of fluralaner against three pests of Henosepilachna vigintioctopunctata, Megalurothrips usitatus, and Phyllotreta striolata in the Solanaceae, Fabaceae, and Cruciferae families, respectively, and the sublethal impact of fluralaner on Propylaea japonica, a widely distributed predatory ladybeetle. Based on LC50, fluralaner was effective against H. vigintioctopunctata (0.098 mg a.i. L−1 for the second instar larvae), M. usitatus (0.134 mg a.i. L−1 for adult females), and P. striolata (0.595 mg a.i. L−1 for adults). For P. japonica, however, fluralaner was substantially less effective (1.177 mg a.i. L−1 for the third instar larvae). Furthermore, the LC10 and LC30 of P. japonica were also consistently higher than the LC50 of the three pests. In addition, we did not observe any significant impacts of fluralaner at LC10 and LC30 on the life history traits, including body weight, developmental time, pre-oviposition period, and fecundity of P. japonica. Based on our results from acute toxicities and sublethal impacts, fluralaner is effective against vegetable pests, while potentially friendly to P. japonica when employed as a biological control agent.

Tripterine is one of the main active components in tripterygium wilfordii polyglycosides tablets. Cyclosporine A (CsA) is an immunosuppressive agent commonly used in clinical organ transplantation. Combined application of Tripterygium wilfordii and cyclosporine A has been proved to enhance the immunosuppressive effect of cyclosporine and reduce its toxic effects. The present study investigated the effect of tripterine on the pharmacokinetics of CsA and its underlying mechanisms.LC-MS/MS was used to establish a detection method of the concentration of CsA in rat blood. Polymerase Chain Reaction (PCR) and Western Blot (WB) were used to determine the expression of tripterine on drug metabolizing enzymes (DMEs), drug transporters (DTs) and nuclear receptors (NRs). As the result, tripterine reduced the bioavailability of cyclosporin A. Compared with control group, the Cmax of CsA were reduced in all dosages of tripterine, and the AUC was significantly decreased in 18 mg∙kg-1 and 54mg∙kg-1 group. The results of PCR and WB showed that tripterine had inhibitory effects on CYP3A1, CYP3A2, UGT1A1, OATP1B2, P-GP, MRP2, BCRP, BSEP and NTCP. Therefore, we put forward that the inhibition effect of tripterine on NTCP, BESP and OATP1B2 in the liver could limit the uptake of cyclosporin A into the blood and the hepatointestinal circulation of cyclosporine A, resulting in the decrease of blood drug concentration of cyclosporin A.

Cell death is a vital event in life. Infections and injuries cause lytic cell death, which gives rise to danger signals that can further induce cell death, inflammation, and tissue damage. The mevalonate (MVA) pathway is an essential, highly conserved and dynamic metabolic pathway. Here, we discover that farnesyl pyrophosphate (FPP), a metabolic intermediate of the MVA pathway, functions as a newly identified danger signal to trigger acute cell death leading to neuron loss in stroke. Harboring both a hydrophobic 15-carbon isoprenyl chain and a heavily charged pyrophosphate head, FPP leads to acute cell death independent of its downstream metabolic pathways. Mechanistically, extracellular calcium influx and the cation channel transient receptor potential melastatin 2 (TRPM2) exhibit essential roles in FPP-induced cell death. FPP activates TRPM2 opening for ion influx. Furthermore, in terms of a mouse model constructing by middle cerebral artery occlusion (MCAO), FPP accumulates in the brain, which indicates the function of the FPP and TRPM2 danger signal axis in ischemic injury. Overall, our data have revealed a novel function of the MVA pathway intermediate metabolite FPP as a danger signal via transient receptor potential cation channels., Farnesyl pyrophosphate, a metabolic intermediate of the cholesterol synthesis pathway, functions as a novel danger signal to trigger acute cell necrosis, and collaborates with activation of the cation channel TRPM2 to play an important role in brain ischemic injury.

Quercetin is a flavonoid that is widely present in plant-derived food. Quercetin-3-O-β-D-glucoside (Q3GA) is a predominant metabolite of quercetin in animal and human plasma. The inhibitory effects of the UDP-glucuronosyl transferases (UGTs) caused by herbal components may be a key factor for the clinical assessment of herb-drug interactions (HDIs). The present study aimed to investigate the inhibitory profile of quercetin and Q3GA on recombinant UGT1A isoforms in vitro. The metabolism of the nonspecific substrate 4-methylumbelliferone (4-MU) by the UGT1A isoforms was assessed by liquid chromatography-tandem mass spectrometry. Preliminary screening experiments indicated that quercetin exhibited stronger inhibitory effects on UGT1A1, UGT1A3, UGT1A6 and UGT1A9 enzymes than Q3GA. Kinetic experiments were performed to characterize the type of inhibition caused by quercetin and Q3GA towards these UGT isoforms. Quercetin exerted non-competitive inhibition on UGT1A1 and UGT1A6, with half maximal inhibitory concentration (IC50) values of 7.47 and 7.07 µM and inhibition kinetic parameter (Ki) values of 2.18 and 28.87 µM, respectively. Quercetin also exhibited competitive inhibition on UGT1A3 and UGT1A9, with IC50 values of 10.58 and 2.81 µM and Ki values of 1.60 and 0.51 µM, respectively. However, Q3GA displayed weak inhibition on UGT1A1, UGT1A3 and UGT1A6 enzymes with IC50 values of 45.21, 106.5 and 51.37 µM, respectively. In the present study, quercetin was a moderate inhibitor of UGT1A1 and UGT1A3, a weak inhibitor of UGT1A6, and a strong inhibitor on UGT1A9. The results of the present study suggested potential HDIs that may occur following quercetin co-administration with drugs that are mainly metabolized by UGT1A1, UGT1A3 and UGT1A9 enzymes.

Previous studies indicate that the transcription factor upstream stimulating factor 1 (USF1) is involved in the regulation of lipid and glucose metabolism. However, the role of USF1 in lipid-induced autophagy remains unknown. Interestingly, we found that USF1 overexpression suppresses autophagy-related gene expression in HepG2 cells. Further assays confirmed that USF1 could transcriptionally activate mTOR expression, thereby suppressing rapamycin-induced autophagy in HepG2 cells. Moreover, pharmacological activation of autophagy with rapamycin decreases the numbers and sizes of lipid droplets (LDs) in HepG2 cells exposed to an oleate/palmitate mixture. Of note, USF1 upregulation decreases colocalization of LDs and autophagosomes. In conclusion, our data provide evidence that USF1 contributes to abnormal lipid accumulation in the liver by suppressing autophagy via regulation of mTOR transcription.

A series of Ce/Fe-Zr-SO42- catalysts have been prepared and developed for selective catalytic reduction of NO with ammonia (NH3-SCR). The catalysts were characterized by XRD, H2-TPR, N2 adsorption-desorption, NH3-TPD and DRIFTS. The characterization results demonstrated that the coexistence of cerium and sulfuric acid on Fe-Zr catalyst could contribute to excellent SCR performance. Among all samples, Ce/Fe-Zr-0.3 S catalyst showed the optimal NOX conversion, reaching more than 80% at 250 °C at a GHSV of 60000 h-1. Moreover, the optimum concentration of SO42- to modify Ce/Fe-Zr catalyst was 0.3 mol/L. The low sulfuric acid concentration contributed to improving low-temperature activity, while high concentration leaded to outstanding high-temperature activity. According to H2-TPR and NH3-TPD, the presence of SO42- increased the total amount of acid sites and more stable sulfate species were formed with higher concentration of sulfuric acid. In situ DRIFTS revealed the NH3 molecule was mainly activated at the Lewis acid site and reacted with the adsorbed NOX species (such as bidentate nitrates) to produce N2 and H2O, which conformed to the L-H reaction mechanism.

Biomass materials have attracted extensive attention in functional composites because of the unique microstructure, renewability and electrochemical performance. Herein, porous NiO/C composites were synthesized through a hydrothermal reaction and calcination using cellulose-rich natural cotton as carbon source. The BET specific surface area of NiO/C composites was calculated to be 314.4 m2 g−1 basing on the Brunauer–Emmett–Teller model. As the LIB anode, NiO/C composites presented a high specific capacity of 727 mA h g−1 over 150 cycles at 100 mA g−1. Increasing the current density to 2 A g−1, enabled the specific capacity of NiO/C the electrode to reach 476 mA h g−1. Obviously, the unique nanostructure and synergistic effect of NiO and carbonaceous matrix made NiO/C composites exhibit the excellent lithium storage performance. The NiO/C composites are interconnected with each other and form nanopores leading to the large specific surface area, enabling the enhancement of electrolyte diffusion and providing additional routes for ion diffusion. In addition, the hybridized carbon substrate can mitigate the volume expansion and external bending stress of NiO/C composites during the lithiation/delithiation process.

Introduction: In breast cancer the androgen receptor (AR) is the most abundantly expressed steroid receptor with 75-95% of estrogen receptor (ER)-positive and 40-70% of ER-negative breast cancers expressing the AR. Historically, advanced breast cancer has been treated with androgens, resulting in significant clinical response. However, the use of steroidal androgens fell from favor as a result of their virilizing side effects. Nonsteroidal, tissue selective androgen receptor modulators (SARMs) will provide a novel targeted approach to exploit the therapeutic benefits of androgens in breast cancer. Aims: To test the effects of enobosarm (a first-in-class SARM) and enzalutamide (AR antagonist) on the growth of patient-derived breast cancer xenografts (PDX) and to discern the mechanism of action of AR-targeted therapies in AR-positive breast cancer. Materials and Methods: AR-positive PDXs with varying receptor expression (ER, progesterone receptor (PR), and HER2) were implanted in immunecompromised mice. Mice carrying PDXs were treated with vehicle, 10 mg/kg/day (mpk) enobosarm (GTx, Inc., Memphis, TN), or 20 mpk enzalutamide (Medivation Inc.), orally. Tumor volume was measured twice or thrice weekly. Tumors that received enobosarm were further analyzed to determine the mechanism of action. Results: Enobosarm significantly (p Conclusion: These results indicate that AR-positive breast cancers are highly heterogeneous and that enobosarm has promise as novel targeted therapy to treat AR-positive breast cancer. Enobosarm is currently in phase II clinical trial in both ER-positive breast cancer and in TNBC patients. Citation Format: Narayanan R, Ponnusamy S, Fan M, Yang CH, Grimes BL, Fleming MD, Pritchard EF, Berry MP, Oswaks RM, Fine RE, Loiseau J-C, Schwartzberg LS, Pfeffer LM. Nonsteroidal, tissue selective androgen receptor modulator (SARM), enobosarm, reduces growth of androgen receptor-positive breast cancer in patient-derived preclinical models [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-12-06.

Chronic cerebral hypoperfusion (CCH) is associated with cognitive decline in aging, Alzheimer's disease and vascular dementia. Neural oscillations and their interactions support brain communication and involve in cognitive function. Although arginine vasopressin (AVP) has been linked to spatial learning and memory, the effects of AVP on CCH in terms of the hippocampal neural network is unknown. Here we investigated the dynamics of neural oscillations in the hippocampus in a rat model of permanent bilateral carotid arteries occlusion (two-vessel occlusion, 2VO) under urethane-anesthesia. Hypertonic saline (5.3%) was injected intraperitoneally to induce the endogenous AVP, and SR49059 was used as V1a receptor (an AVP receptor) antagonist. The results showed that AVP partly changed CA3 Schaffer collateral (CA3-SC) power distribution in the rat model of 2VO via V1a receptor, increased theta synchrony between CA3-SC and CA1 areas, enhanced CA3-SC theta-middle gamma phase-phase coupling, and improved spatial learning and memory performance. Biochemical fractionation further confirmed the recovery effect on N-methyl-D-aspartate receptor subunit 2B (NR2B) and postsynaptic density protein 95 (PSD-95) surface expressions after hypertonic saline injection, suggesting a possible molecular mechanism in the hippocampus. The findings shed light on a functional role of endogenous AVP from a neural network perspective that AVP improves theta synchronization and accurate coordination of theta-gamma coupling probably through upregulating NR2B and PSD-95 expressions, and further promotes neural communication in the hippocampus to some extent. As a result, the impairment of spatial learning and memory induced by CCH is significantly alleviated.

Co3O4 is considered a promising anode candidate for lithium ion batteries (LIBs) owing to its high theoretical capacitance. However, the electrochemical properties of bare Co3O4 for LIBs remain seriously limited by poor electronic conductivity and large volume expansion. Herein, carbon-coated porous Co3O4 polyhedrons with (220) facets are fabricated through a hydrothermal method and subsequent calcination process. The size of Co3O4 polyhedrons ranges from 70 nm to 170 nm. The continuous amorphous carbon layer is approximately 3 nm thick, and uniformly covers the surface of Co3O4. Moreover, the discharge capacity of carbon-coated porous Co3O4 anode reaches 1463 and 596 mA h g−1 at 100 and 5000 mA g−1, respectively. After 150 charge discharge cycles, the carbon-coated Co3O4 anode still exhibits a reversible capacity of 840 mA h g−1 at 1000 mA g−1. Carbon nano-coating, mixed conductive matrix, and crystalline texture design can enhance the electrochemical performance of Co3O4.

Vascular dementia (VD) is the second most common cause of cognitive impairment in the elderly population. Our study aims to investigate the neuroprotective effects of glycyrrhizic acid (GA), a major active constituent of Glycyrrhiza glabra root, in a VD rat model induced by permanent occlusion of the bilateral common carotid arteries. Spatial cognitive function was examined by the Morris water maze test and synaptic plasticity was explored by assessing long-term potentiation. The results showed that GA (20 mg/kg for 5 days) significantly improved the performance of learning and memory of VD rats in the Morris water maze test and attenuated induction of long-term potentiation. Histopathological studies showed that GA significantly attenuated cell damage in VD rats. Malondialdehyde levels and superoxide dismutase activity were analyzed in the hippocampus and cortex to investigate anti-oxidant status. The results showed that GA decreased the level of lipid peroxidation and increased the activity of superoxide dismutase in VD rats. Lastly, whole-cell patch-clamp analysis was used to examine the effect of GA on voltage-gated sodium channels (VGSCs) in hippocampal CA1 pyramidal neurons. GA (10, 20 and 50 μM) inhibited the current amplitude of the VGSCs. These results suggest that the neuroprotective e.ects of GA in VD rats relate to the reduction of oxidative stress and inhibition of VGSCs. Our study provides experimental evidence for the application of GA in the treatment of cognitive deficits induced by Alzheimer's disease, stroke, or traumatic brain injury.

The aim of the present study was to evaluate whether quercetin (Que) modulates the mRNA and protein expression levels of drug-metabolizing enzymes (DMEs) and drug transporters (DTs) in the small intestine and liver, and thus modifies the pharmacokinetic profile of cyclosporine (CsA) in rats. This two-part study evaluated the pharmacokinetic profiles of CsA in the presence or absence of Que (experiment I) and the involvement of DMEs and DTs (experiment II). In experiment I, 24 rats received single-dose CsA (10 mg/kg) on day 1, single-dose Que (25, 50 and 100 mg/kg/day; eight rats in each group) on days 3–8, and concomitant CsA/Que on day 9. In experiment II, the mRNA and protein expression levels of cytochrome P (CYP)3A1, CYP3A2, UDP glucuronosyltransferase family 1 member A complex locus, organic anion-transporting polypeptide (OATP)2B1, OATP1B2, P-glycoprotein, breast cancer resistance protein, and multidrug resistance-associated protein 2 in the small intestine and liver of rats were analyzed following oral administration of Que at 25, 50 and 100 mg/kg in the presence or absence of CsA (10 mg/kg) for seven consecutive days. Co-administration of Que (25,50 and 100 mg/kg) decreased the maximum serum concentration of CsA by 46, 50 and 47% in a dose-independent manner. In addition, the area under the curve to the last measurable concentration and area under the curve to infinite time were decreased, by 21 and 16%, 30 and 33%, and 33 and 34% (P

Biomass-derived porous carbon BPC-700, incorporating micropores and small mesopores, was prepared through pyrolysis of banana peel followed by activation with KOH. A high specific BET surface area (2741 m2 g-1 ), large specific pore volume (1.23 cm3 g-1 ), and well-controlled pore size distribution (0.6-5.0 nm) were obtained and up to 65 wt % sulfur content could be loaded into the pores of the BPC-700 sample. When the resultant C/S composite, BPC-700-S65, was used as the cathode of a Li-S battery, a large initial discharge capacity (ca. 1200 mAh g-1 ) was obtained, indicating a good sulfur utilization rate. An excellent discharge capacity (590 mAh g-1 ) was also achieved for BPC-700-S65 at the high current rate of 4 C (12.72 mA cm-2 ), showing its extremely high rate capability. A reversible capacity of about 570 mAh g-1 was achieved for BPC-700-S65 after 500 cycles at 1 C (3.18 mA cm-2 ), indicating an outstanding cycling stability.

A simple strategy for the reduction of graphene oxide by annealing was used to produce 3D hierarchically interconnected porous graphene (HIPG) samples. The optimized HIPG-900 sample possessing a specific surface area of 367.4 m2 g−1 and pore volume of 1.3 cm3 g−1 contains a large amount of sulfur (65.8 wt %) and improves the utilization of sulfur when used as the cathode of Li–S batteries. A high initial specific discharge capacity of 914.1 mAh g−1 and a specific capacity of 486.0 mAh g−1 after 500 cycles was obtained for HIPG-900/S composites at 1C. A high specific capacity of 467.2 and 162.4 mAh g−1 was obtained at a high rate of 10C with a Coulombic efficiency of over 90.0 % at the 1st and 500th cycle, respectively.

Neuronal apoptosis is a central hallmark of cerebral ischemia, which is serious threats to human health. Notch1 signaling pathway and three members of miR-200 family, miR-429, miR-200a and miR-200b, are reported to have tight connection with hypoxia-induced injury. However, their mutual regulation relationship and their roles in neuronal apoptosis caused by hypoxia are rarely reported. In the present study, differentiated pheochromocytoma (PC12) cells were treated with chemical hypoxia inducer, cobalt chloride (CoCl2) to establish in vitro neuronal hypoxia model. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, Western blot assay and Hoechst staining indicated that CoCl2 caused apoptosis of PC12 cells along with the activation of Notch1 signallilng pathway. The treatment of N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butylester (DAPT) inhibited Notch1 signaling pathway and attenuated the apoptosis induced by CoCl2. Real-time polymerase chain reaction (RT-PCR) showed that expressions of miR-429/200a/200b were dynamically changed during the treatment of CoCl2, and significantly decreased after 12-hour treatment of CoCl2. Overexpression of miR-429/200a/200b inhibited the Notch1 signaling pathway and suppressed CoCl2-induced apoptosis in PC12 cells. These results may clarify the roles of miR-429/200a/200b and Notch1 signaling pathway in hypoxia-induced nerve injury and provide a new theoretical basis to relieve nerve injury.

Quercetin is a flavonoid compound that is widely present in food and drink. Quercetin‑3‑O‑β‑D‑glucoside (Q3GA) is a major metabolite of quercetin. The aim of the present study was to investigate the effect of Q3GA on the pharmacokinetics of orally and intravenously administered cyclosporin A (CsA) in rats, and to assess the effect of Q3GA on drug‑metabolizing enzymes (DMEs), drug transporters (DTs) and nuclear receptors (NRs). The pharmacokinetic parameters of CsA were measured following oral (10 mg/kg) and intravenous (2.5 mg/kg) administration of CsA in the presence or absence of Q3GA. The mRNA and protein expression levels of DMEs, DTs and NRs in the liver and small intestine were detected by quantitative polymerase chain reaction and western blot analysis. The results indicated that the intravenous administration of Q3GA (2.5, 5 or 10 mg/kg) for 7 consecutive days reduced the bioavailability of oral CsA. By contrast, the pharmacokinetics of the intravenous administration of CsA were not affected by Q3GA. However, the mRNA and protein expression levels of DMEs and DTs were inhibited by Q3GA. The activation of DMEs and DTs by NRs, and the interplay between DMEs and DTs, may explain these results. The present study identified a novel flavonoid‑drug interaction, which may have implications for patients taking CsA and quercetin supplements or on a quercetin‑containing diet.

The primary aim of the present study was to evaluate the effects of liraglutide on glucolipotoxicity-induced liver cell apoptosis and the underlying mechanisms in Zucker diabetic fatty (ZDF) rats. The results revealed that liraglutide significantly decreased the body weight, hyperglycemia and hyperlipidemia of ZDF rats relative to those of Zucker lean (ZL) rats (P

Gap junction protein beta-1 (GJB1) gene mutations lead to X-linked Charcot-Marie-Tooth Type 1 (CMTX1). We studied a Chinese family with CMTX1 and identified a novel GJB1 point mutation. Our patient had a transient stroke-like clinical manifestations and magnetic resonance imaging (MRI) changes. An analysis of the genomic DNA of the proband showed a T to C hemizygous mutation in the GJB1 gene at nucleotide position 380, causing a predicted amino acid change from isoleucine to threonine at codon 127, which predicted structural alterations disrupting the function of the GJB1 protein. This novel point mutation expanded the spectrum of GJB1 mutations known to be associated with CMTX1. We performed a PubMed review of CMTX cases with central nervous system involvement in the English-language literature from the past 20 years, and summarized the demographic data, nucleotide and amino acid changes, clinical characteristics, clinical manifestations, and neuroimaging features.

Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) is a reliable technique commonly used in molecular biology to analyze RNA expression. The selection of suitable reference genes for data normalization is a precondition for credible measurements of gene expression levels using RT-qPCR. Propylea japonica is one of the most common pests of many crop systems throughout East Asia, and has often been used in the testing of non-target impacts during environmental risk assessments of genetically engineered plants. The present study assessed the suitability of nine frequently used reference genes for comparisons of P. japonica gene expression. Expression stability was compared across developmental stages, sex, a range of tissues, and following exposure to different temperatures. Data were analyzed using RefFinder, which integrated the results obtained using NormFinder, geNorm, BestKeeper, and the ΔCt method. This led to the identification of unique sets of reference genes for each experimental condition: ribosomal protein S18 (RPS18) and elongation factor 1 α (EF1A) for developmental stage comparisons, RPS18 and EF1A for sex comparisons, EF1A and ribosomal protein L4 for tissue comparisons, and RPS18 and EF1A for analyses of temperature-mediated effects. These reference genes will help to enhance the accuracy of RT-qPCR analyses of P. japonica gene expression. This work represents an initial move towards building a standardized system for RT-qPCR analysis of P. japonica, providing a basis for the ecological risk assessment of RNAi-based insect control products.

It is well known that the neuronal effects of vascular endothelial growth factor (VEGF) include modulating learning and memory, plasticity of mature neurons, and synaptic transmission in addition to neurogenesis. However, there is conflicting evidence particularly of its role in the regulation of excitatory synaptic activity. In this study, application of the patch-clamp technique revealed that lower doses (10 and 50 ng/mL) of VEGF enhanced excitatory neurotransmission in hippocampal slices of mice through both presynaptic and postsynaptic mechanisms. However, the effects were reversed by higher doses of VEGF (>100 ng/mL), which inhibited excitatory neurotransmission via a presynaptic mechanism. These competing, concentration-dependent effects of VEGF suggested that different pathways were involved. The involvement of the Notch1 receptor was tested in the modulation of VEGF on synaptic activity by using heterozygous Notch1(+/-) mice. Notch1 knockdown did not influence the inhibitory effect of high VEGF doses (200 ng/mL) but reduced the enhancement effects of low concentration of VEGF (50 ng/mL) at the postsynaptic level, which might be due to the decreased level of VEGF receptor. The results indicate that the Notch1 receptor plays a role in VEGF-induced modulation of synaptic activity, which provides new insights into a complex VEGF/Notch signaling cross-talk. These findings set the groundwork for understanding new mechanisms of Notch signaling and the neurotrophic effects of VEGF, which is beneficial to develop new therapeutic targets to the VEGF/Notch axis and improve current treatments for neural diseases.

Unique activated carbon (AAC) is prepared by pyrolysis of natural waste Apricot shell following with KOH activation. The facile and cost-effective bio-inspired method possesses a high product yield of 40.7 wt%. The AAC sample has a high BET surface area of 2269 m 2 g −1 and large pore volume of 1.05 cm 3 g −1 , which is beneficial to effectively hold the sulfur and restrain the diffusion of polysulfides during the galvanostatic charge/discharge processes using as the cathode matrix for the rechargeable Li–S battery. The pore size distribution of the AAC sample is ranging from 0.6 to 2.0 nm, which leads to the nonconductive sulfur being loaded into the micropores of the carbon matrix in highly dispersed state, having and/or losing electrons easily at the same time. The optimized AAC/S composite material shows an excellent cycle performance and a good rate capability when using as the cathode in Li–S battery. The initial discharge capacity of 1277 mAh g −1 can be obtained at 0.1 C. A stable discharge capacity of about 710 mAh g −1 at a current density of 0.2 C and the discharge capacity of 613 mAh g −1 at a high current density of 1 C may be achieved after 200 charge/discharge cycles.

Bio-inspired beehive-like hierarchical nanoporous carbon (BHNC) with a high specific surface area of 1472 m2 g−1 and a good electronic conductivity of 4.5 S cm−1 is synthesized by carbonizing the industrial waste of bamboo-based by-product. The BHNC sample exhibits remarkable electrochemical performances as a supercapacitor electrode material, such as a high specific capacitance of 301 F g−1 at 0.1 A g−1, still maintaining a value of 192 F g−1 at 100 A g−1, negligible capacitance loss after 20 000 cycles at 1 A g−1, and a high power density of 26 000 W kg−1 at an energy density of 6.1 W h kg−1 based on active electrode materials in an aqueous electrolyte system. Moreover, an enhanced power density of 42 000 W kg−1 at a high energy density of 43.3 W h kg−1 is obtained in an ionic liquid electrolyte system, which places the BHNC-based supercapacitors in the Ragone chart among the best energy–power synergetic outputting properties ever reported for carbon-based supercapacitors.

Several studies have suggested an important role of miR-291b-3p in the development of embryonic stem cells. In previous study, we found that the expression of miR-291b-3p was significantly upregulated in the liver of db/db mice. However, the role of miR-291b-3p in glucose metabolism and its underlying mechanisms remain unknown. In the present study, we demonstrated that miR-291b-3p was abundantly expressed in the liver. Of note, hepatic miR-291b-3p expression was upregulated in HFD-fed mice and induced by fasting in C57BL/6 J normal mice. Importantly, hepatic inhibition miR-291b-3p expression ameliorated hyperglycemia and insulin resistance in HFD-fed mice, whereas hepatic overexpression of miR-291b-3p led to hyperglycemia and insulin resistance in C57BL/6 J normal mice. Further study revealed that miR-291b-3p suppressed insulin-stimulated AKT/GSK signaling and increased the expression of gluconeogenic genes in hepatocytes. Moreover, we identified that p65, a subunit of nuclear factor-κB (NF-κB), is a target of miR-291b-3p by bioinformatics analysis and luciferase reporter assay. Silencing of p65 significantly augmented the expression of PTEN and impaired AKT activation. In conclusion, we found novel evidence suggesting that hepatic miR-291b-3p mediated glycogen synthesis and gluconeogenesis through targeting p65 to regulate PTEN expression. Our findings indicate the therapeutic potential of miR-291b-3p inhibitor in hyperglycemia and insulin resistance.

Superhydrophilicity of TiO2 thin film under natural conditions is of great importance for antifogging and self-cleaning applications of glass products. Transparent superhydrophilic porous ZnO/TiO2 composite films were prepared on glass substrates using a template-free sol–gel method. The results indicated that the porous ZnO (10%)/TiO2 composite film possesses superhydrophilicity with water contact angle less than 5° without UV irradiation. Surface chemical composition of the films was characterized by X-ray photoelectron spectroscopy (XPS). The morphologies of the porous films were characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM). The porous morphology, crystal structure and surface chemical composition were significantly affected by ZnO addition. The natural superhydrophilic performance was attributed to the synergistic effect of the porous structure and surface hydroxyl groups. Photocatalytic activities of the ZnO/TiO2 composites were also evaluated using methyl orange (MO) as a model pollutant, with 78.1% of MO degraded by ZnO (10%)/TiO2, which was higher than 49.3% obtained from pure TiO2.

A facile synthesis of an MnO/C nanocomposite material consisting of 5.3 wt% of MnO on the surface of porous carbon is introduced. Equally distributed nanosized MnO particles and the porous carbon matrix have fully developed a synergistic effect to achieve superior lithium ion storage performance. Using the MnO/C nanocomposite material as the anode of a Li-ion battery, a high discharge capacity of 952 mA h g−1 has been obtained at a current density of 0.1 A g−1 with a stable cycling performance over 100 charge–discharge cycles.

A novel one-step hydrothermal and calcination strategy was developed to synthesize the unique 1D oriented Co3O4 crystal nanofibers with (220) facets on the carbon matrix derived from the natural, abundant and low cost wool fibers acting as both carbon precursor and template reagent. The resultant W2@Co3O4 nanocomposite exhibited very high specific capacity and favorable high-rate capability when used as anode material of lithium ion battery. The high reversible Li+ ion storage capacity of 986 mAh g−1 was obtained at 100 mA g−1 after 150 cycles, higher than the theoretical capacity of Co3O4 (890 mAh g−1). Even at the higher current density of 1 A g−1, the electrode could still deliver a remarkable discharge capacity of 720 mAh g−1 over 150 cycles.

One-dimensional (1D) hierarchical porous nanofibers of Co3O4 possessing of (220) facets on the carbon matrix from human hair (H2@Co3O4) with 20–30 nm in width and 3–5 μm in length are prepared by a facile solvothermal and calcination approach. The well crystallized small Co3O4 particles with the diameter of about 8–12 nm were closely aggregated together in the nanofibers. Electrochemical analyses show that the first discharge capacity of H2@Co3O4 electrode is 1368 mAh g−1 at the current density of 0.1 A g−1 based on the total mass of composite. A high reversible capacity of 916 mAh g −1 was obtained over 100 cycles at 0.1 A g−1, presenting a good cycling stability. When cycled at a high current density of 1 and 2 A g−1, the specific capacity of 659 and 573 mAh g−1 could be still achieved, respectively, indicating a superior power capability.