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In this paper, Ni2P nanoparticles is incorporated onto the graphene & carbon nanotubes composite (Ni2P NPs/rGO & CNTs) to form flexible free-standing intertwining network film anodes for improving the cycle-life of sodium-ion batteries (SIBs). Benefited from the volume accommodation by this Ni2P NPs/rGO & CNTs structure and its excellent electronic conductive network along with high mechanical strength, such an anode-based SIB shows a superior capacity retention with a stable and long cycle-life at high current densities. For Ni2P NPs/rGO & CNTs electrode, it remains a capacity of 224 mAh g−1 after 100 cycles, at a high current density of 0.5 A g−1, the Ni2P NPs/rGO & CNTs can still maintain a stable reversible capacity of ~ 150 mAh g−1 after 500 cycles, after cycling at a rate as high as 1 A g−1, the reversible capacity of the Ni2P NPs/rGO/CNT can still sustain stable capacities at 91 mAh g−1 after 2000 cycles, respectively. Even at 5 A g−1, it still exhibits a high rate capacity of 65 mAh g−1, thus exhibiting an excellent sodium storage kinetics.

Neural stem/progenitor cells (NSPCs) persist in the mammalian subventricular zone throughout life, where they can be activated in response to physiological and pathophysiological stimuli. A recent study indicates metabotropic glutamate receptor 4 (mGluR4) is involved in regulating NSPCs behaviors. Therefore, defining mGluR4 function in NSPCs is necessary for determining novel strategies to enhance the intrinsic potential for brain regeneration after injuries. In this study, mGluR4 was functionally expressed in SVZ-derived NSPCs from male Sprague-Dawley rats, in which the cyclic adenosine monophosphate concentration was reduced after treatment with the mGluR4-specific agonist VU0155041. Additionally, lateral ventricle injection of VU0155041 significantly decreased 5-bromo-2'-deoxyuridine (BrdU)+ and Ki67+ cells, while increased Doublecortin (DCX)/BrdU double-positive cells in SVZ. In cultured NSPCs, mGluR4 activation decreased the ratio of BrdU+ cells, G2/M-phase cells, and inhibited Cyclin D1 expression, whereas it increased neuron-specific class III β-tubulin (Tuj1) expression and the number of Tuj1, DCX, and PSA-NCAM-positive cells. However, pharmacological blocking mGluR4 with the antagonist MSOP or knockdown of mGluR4 abolished the effects of VU0155041 on NSPCs proliferation and neuronal differentiation. Further investigation demonstrated that VU0155041 treatment down-regulated AKT phosphorylation and up-regulated expression of the phosphatase and tensin homolog protein (PTEN) in NSPCs culture. Moreover VU0155041-induced proliferating inhibition and neuronal differentiating amplification in NSPCs were significantly hampered by VO-OHpic, a PTEN inhibitor. We conclude that activation of mGluR4 in SVZ-derived NSPCs suppresses proliferation and enhances their neuronal differentiation, and regulation of PTEN may be involved as a potential intracellular target of mGluR4 signal. Cover Image for this issue: https://doi.org/10.1111/jnc.15052.

Background UBTF is an HMGB-box DNA binding protein and a necessary Pol I/Pol II basal transcription factor. It has been found that UBTF involves in carcinogenesis and progression of a few cancers. Nevertheless, the the biological function and potential molecular mechanism of UBTF in melanoma are still not clear and need to be clarified. Methods UBTF and GIT1 expressions in melanoma specimens and cell lines were examined by quantitative real-time PCR (qRT-PCR) and Western blot. MTT and colony formation assays were used to investigate the effects of UBTF and GIT1 on melanoma cell proliferation. Cell cycle and apoptosis assays were detected by flow cytometry. Tumor formation assay was used to analyze the effect of UBTF on melanoma growth. Bioinformatics predicting, chromatin immunoprecipitation (ChIP)-qRT-PCR and reporter gene assay were fulfilled for verifing GIT1 as UBTF targeting gene. Results Here we reported that UBTF mRNA and protein expressions were upregulated in primary melanoma specimens and cell lines. UBTF overexpression facilitated melanoma cell proliferation and cell cycle progression and restrained. Silencing UBTF suppressed cell multiplication, cell cycle progression and tumor growth, and promoted apoptosis. UBTF expression was positively related with GIT1 expression in human melanoma tissues. It was verified that UBTF promoted GIT1 transcription in melanoma cells through binding to the promoter region of GIT1. Furthermore, GIT1 overexpression promoted melanoma cell growth and suppressed apoptosis. Knockdown of GIT1 inhibited cell multiplication and induced apoptosis. Overexpression of GIT1 eliminated the effects of silencing UBTF on melanoma cells. Importantly, UBTF activated MEK1/2-ERK1/2 signalling pathways by upregulating GIT1 expression. Conclusions Our study demonstrates that UBTF promotes melanoma cell proliferation and cell cycle progression by promoting GIT1 transcription, thereby activating MEK1/2-ERK1/2 signalling pathways. The findings indicate that UBTF plays a crucial function in melanoma and may be a potential therapeutic target for the treatment of this disease.

A class of unimolecular channels formed by pillararene-gramicidin hybrid molecules are presented. The charge status of the peptide domain in these channels has a significant impact on their ion transport and antimicrobial activity. These channels exhibited different membrane-association abilities between microbial cells and mammalian cells. One of the channels displayed a higher antimicrobial activity towards S. aureus (IC50 = 0.55 μM) and negligible hemolytic toxicity, showing potential to serve as a systemic antibiotic.

Grain growth can modify the texture orientation and the fraction of different texture component. The thermal stability of two texture component in an extruded magnesium AZ31 alloy was investigated. Three types samples with different texture distribution were prepared. The results show that normal grain growth takes place in the magnesium AZ31 alloy during annealing at 300 °C and 450 °C. But the grain growth does not lead to the strengthening of either texture component. Both the ⊥ED texture and //ED texture components show good thermal stability, without influence of the texture volume fraction. The two different texture component possess comparable boundary migration ability, so grains of the two texture component consume indifferently the other grains, or are equally consumed during annealing. Keywords: Mg alloy, Texture, Thermal stability, Grain growth annealing, Twinning

MicroRNAs (miRNAs) play critical roles in the tumorigenesis and progression of gastric cancer (GC). However, the biological function of miR-4268 in GC and its mechanism remain unclear. In the present study, qTR-PCR found that the expression of miR-4268 was significantly downregulated in GC tissues and cell lines. The overexpression of miR-4268 inhibited GC cell proliferation and the cell cycle G1/S phase transition, and induced cell apoptosis. In contrast, inhibition of miR-4268 promoted cell proliferation and G1-S transition, and suppressed cell apoptosis. Further analyses revealed that miR-4268 expression was negatively correlated with Rab6B expression in GC tissues. Rab6B was verified to be a direct target of miR-4268. Notably, silencing Rab6B resulted in the same biological effects in GC cells as those induced by overexpression of miR-4268. Importantly, both miR-4268 overexpression and Rab6B silence inhibited the AKT/JNK signaling pathways, which modulated cell cycle regulators (Cyclin D1 and CDK4). In contrast, inhibition of miR-4268 promoted the AKT/JNK signaling pathways. MiR-4268 overexpression also promoted the p38 MAPK signaling pathway. Taken together, miR-4268 suppresses GC cell proliferation through inhibiting the AKT/JNK signaling pathways by targeting Rab6B and induces cell apoptosis through promoting the p38 MAPK signaling pathway. Our findings indicate a tumor-suppressor role of miR-4268 in GC pathogenesis and the potential of miR-4268 in GC theropy.

A class of artificial K+ channels formed by pillararene-cyclodextrin hybrid molecules have been designed and synthesized. These channels efficiently inserted into lipid bilayers and displayed high selectivity for K+ over Na+ in fluorescence and electrophysiological experiments. The cation transport selectivity of the artificial channels is tunable by varying the length of the linkers between pillararene and cyclodexrin. The shortest channel showed specific transmembrane transport preference for K+ over all alkali metal ions (selective sequence: K+ > Cs+ > Rb+ > Na+ > Li+ ), and is rarely observed for artificial K+ channels. The high selectivity of this artificial channel for K+ over Na+ ensures specific transmembrane translocation of K+ , and generated stable membrane potential across lipid bilayers.

Pregnancy Associated Malaria (PAM) threatens more than one million pregnant women and their infants in endemic regions due to poor outcomes, such as maternal anemia, stillbirth, infant death, etc. VAR2CSA, a 350 kDa transmembrane protein encoded by Plasmodium falciparum (P.falciparum), plays a vital role in the cytoadherence of infected erythrocytes (IEs) to placenta. Chondroitin sulfate A (CSA), displayed mostly on the surface of placental or tumor cells, has been recognized as the specific ligand for VAR2CSA. However, the architecture and CSA binding mechanism of VAR2CSA remain elusive. In this study, we determined the cryo-EM structures of P. falciparum VAR2CSA ectodomain and its complex with CSA at a resolution of 3.6 A and 3.4 A, respectively. Most importantly, it was revealed that CSA binding induces significant conformational change to close the binding pocket by turning DBL2X and DBL1X closer to DBL4e, and meanwhile enlarge the inner binding pocket via slightly moving a CSA-binding helix of DBL2X outward. Impressively, the structural analysis indicated that 9 key residues with positive charge in DBL2X might be mainly responsible for CSA binding, which is further validated by multidisciplinary methods, i.e., sequence alignment, site mutagenesis, CSA binding tests, and cytoadherence assays using confocal fluorescence microscopy. In summary, we elucidated the detailed molecular mechanism of cytoadherence to placenta or tumor cells through VAR2CSA, which may facilitate antigen design for PAM vaccine, and improve the drug delivery systems targeting both placenta and tumors.

At present, conventional microdialysis (MD) techniques cannot efficiently sample lipids in vivo, possibly due to the high mass transfer resistance and/or the serious adsorption of lipids onto the semi-permeable membrane of a MD probe. The in vivo monitoring of lipids could be of great significance for the study of disease development and mechanisms. In this work, an open-flow microperfusion (OFM) probe was fabricated, and the conditions for sampling lipids via OFM were optimized. Using OFM, the recovery of lipid standards was improved to more than 34.7%. OFM is used for the in vivo sampling of lipids in mouse liver tissue with fibrosis, and it is then combined with mass spectrometry (MS) to perform lipidomic analysis. 156 kinds of lipids were identified in the dialysate collected via OFM, and it was found that the phospholipid levels, including PC, PE, and SM, were significantly higher in a liver suffering from fibrosis. For the first time, OFM combined with MS to sample and analyze lipids has provided a promising platform for in vivo lipidomic studies.

This study investigated the effect of methyl-CpG-binding protein 2 (MeCP2) on miRNA transcription. Our results of miRNA chip assay and ChIP-seq showed that MeCP2 inhibited the expressions of numerous miRNAs by binding to their upstream elements, including not only the promoter but also the distal enhancer. Among the affected miRNAs, miR-22 was identified to remarkably suppress gastric cancer (GC) cell proliferation, arrest G1–S cell cycle transition, and induce cell apoptosis by targeting MeCP2, MTHFD2, and MTHFR. Understanding GC metabolism characteristics is the key to developing novel therapies that target GC metabolic pathways. Our study revealed that the metabolic profiles in GC tissues were altered. SAM (S-adenosylmethionine), a universal methyl donor for histone and DNA methylation, which is specifically involved in the epigenetic maintenance of cancer cells, was found increased. The production of SAM is promoted by the folate cycle. Knockdown of MTHFD2 and MTHFR, two key enzymes in folate metabolism and methyl donor SAM production, significantly suppressed GC cell proliferation. MiR-22 overexpression reduced the level of endogenous SAM by suppressing MTHFD2 and MTHFR, inducing P16, PTEN, and RASSF1A hypomethylation. In conclusion, our study suggests that miR-22 was inhibited by MeCP2, resulting in deficiency of endogenous SAM, and ultimately leading to tumor suppressor dysregulation.

Methyl-CpG-binding protein 2 (MeCP2) facilitates the carcinogenesis and progression of several types of cancer. However, its role in breast cancer and the relevant molecular mechanism remain largely unclear. In this study, analysis of the Cancer Genome Atlas (TCGA) data that MeCP2 expression was significantly upregulated in breast cancer tissues, and high MeCP2 expression was correlated with poor overall survival. Knockdown of MeCP2 inhibited breast cancer cell proliferation and G1–S cell cycle transition and migration as well as induced cell apoptosis in vitro. Moreover, MeCP2 knockdown suppressed cancer cell growth in vivo. Investigation of the molecular mechanism showed that MeCP2 repressed RPL11 and RPL5 transcription by binding to their promoter regions. TCGA data revealed significantly lower RPL11 and RPL5 expression in breast cancer tissues; additionally, overexpression of RPL11/RPL5 significantly suppressed breast cancer cell proliferation and G1–S cell cycle transition and induced apoptosis in vitro. Furthermore, RPL11 and RPL5 suppressed ubiquitination-mediated P53 degradation through direct binding to MDM2. This study demonstrates that MeCP2 promotes breast cancer cell proliferation and inhibits apoptosis through suppressing RPL11 and RPL5 transcription by binding to their promoter regions.

The new demands for energy storage systems have been placed with demands for flexible wearable electronics. Herein, rugby-like GeO₂ nanoparticles (NPs) have been directly grown on carbon cloth (GeO₂ NPs/CC) through a one-step hydrolysis process at room temperature, which can be used as a self-supporting flexible anode for lithium ion battery (LIBs). The rugby-like GeO₂ NPs/CC showed an improved lithium-storage performance with features of high reversible capacity ~2000 mA·h·g-1 even after 100 cycles and good cycling stability. Besides, its initial coulomb efficiency (79.1%) was also enhanced compared to that of some reported GeO₂-based materials.

In this work, three-dimensional (3D) TiO₂ nanotubes (NTs) on carbon cloth (CC) (TiO₂ NTs/CC) were synthesized by a method involving formation of a ZnO@TiO₂ nanorod (NRs) on CC (ZnO@TiO₂ NRs/CC) structure and a subsequent chemical etching process for ZnO NRs template. The 3D TiO₂ NTs/CC were applied as flexible anodes for sodium ion batteries (SIBs). The TiO₂ NTs/CC yielded high specific capacity and good cycling stability, superior to that of some reported TiO₂ nanocomposites. The TiO₂ NTs/CC delivered a reversible capacity of 260 mA·h·g-1 and 85.1% capacity retention over 150 cycles at current density of 0.25 C (1 C = 335 mA·g-1). It also exhibited high rate capacity of 200 mA·h·g-1 at 0.5 C. Even at a high rate of 1.0 C, the TiO₂ NTs/CC can still maintain a high capacity of 100 mA·h·g-1. Moreover, it was observed that the electrochemical performance for the TiO₂ NTs/CC was much better than that (150 mA·h·g-1 for up to 150 cycles) of a solid TiO₂ NRs/CC counterpart, which also demonstrated the capacity enhancement and good cycling stability.

Filtering capacitors with high energy densities are of critical importance in stabilizing the pulse signal of circuits that require the conversion of alternating current to direct current, which is however far from satisfactory at current stage due to lack of a reasonable design. Here, we report an ultrafast aqueous electrochemical capacitor based on highly conductive and continuously cross-linked poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) nanomesh films fabricated using a rational morphology engineering strategy. The interpenetrating polymer network promoted an efficient electron transfer and provided smooth channels for ion transport while exposing a significant number of accessible interfacial area to electrolyte. In addition to the large phase angle of − 84° at 120 Hz, this polymer-based electrochemical capacitor exhibited an extremely high areal specific capacitance of 1087 μF cm−2 and areal specific energy density of 544 μF V2 cm−2, far superior to those of most reported aqueous filtering capacitors. Furthermore, it can efficiently smoothen the ripples generated when arbitrary alternating current waveforms were converted into straight signals over a wide frequency range of 1–10,000 Hz. Moreover, it was conveniently integrated with a rotating disk triboelectric nanogenerator for ripple filtering and pulse energy smoothing. This work brings a view for aqueous filtering capacitors with high performance.

Background/Aims: MicroRNAs (miRNAs) have been well studied in human carcinogenesis and cancer progression. Our previous study showed the down-regulation of miR-338-3p expression in human gastric cancer (GC). However, the reasons of this dysregulation remain largely unclear. Methods: Bisulfite sequence analysis was performed to explore the methylation status of the promoter region of miR-338-3p. Cell wound-healing and transwell assays were performed to examine the capacity of cell migration and cell interaction. A dual-luciferase reporter was used to validate the bioinformatics-predicted target gene of miR-338-3p. Western blotting, RNA interference, and immunofluorescence (IF) were used to evaluate the expression of MMPs and the location of N-cadherin to determine the mechanism underlying miR-338-3p-induced anti-tumor effects. Results: miR-338-3p was epigenetically silenced, and this loss of expression was significantly correlated with the Borrmann Stage in GC. Restoring miR-338-3p expression in BGC-823 cells inhibited cell migration and invasion. Moreover, Ras-related protein (Rab-14) and Hedgehog acyltransferase (Hhat) were identified as direct targets of miR-338-3p. Both enforced expression of miR-338-3p and small interfering RNA induced Rab14-mediated accumulation of N-cadherin in the cell -cell junctions or Hhat-associated matrix metalloproteinase (MMP) degradation, which may underline the metastasis defects caused by loss of miR-338-3p in GC. Conclusion: These data indicate that miR-338-3p functions as a tumor suppressor in GC, and that the hypermethylation status of its CpG island might be a novel potential strategy for treating GC.

An efficient ligand- and solvent-free method for the synthesis of quinoxaline derivatives via copper(I)-catalyzed cross-coupling process has been developed. 1,2-Halobenzenes or 1,8-diiodonaphthalene coupled with N,N′-disubstituted ethane-1,2-diamines to give the corresponding products in moderate yields under the reaction conditions.

Background MicroRNAs (miRNAs) play key roles in tumorigenesis and progression of gastric cancer (GC). miR-1269 has been reported to be upregulated in several cancers and plays a crucial role in carcinogenesis and cancer progression. However, the biological function of miR-1269 in human GC and its mechanism remain unclear and need to be further elucidated. Methods The expression of miR-1269 in GC tissues and cell lines was detected by quantitative real-time PCR (qRT-PCR). Target prediction programs (TargetScanHuman 7.2 and miRBase) and a dual-luciferase reporter assay were used to confirm that Ras-association domain family 9 (RASSF9) is a target gene of miR-1269. The expression of RASSF9 was measured by qRT-PCR and Western blotting in GC tissues. MTT and cell counting assays were used to explore the effect of miR-1269 on GC cell proliferation. The cell cycle and apoptosis were measured by flow cytometry. RASSF9 knockdown and overexpression were used to further verify the function of the target gene. Results We found that miR-1269 expression was upregulated in human GC tissues and cell lines. The overexpression of miR-1269 promoted GC cell proliferation and cell cycle G1-S transition and suppressed apoptosis. The inhibition of miR-1269 inhibited cell growth and G1-S transition and induced apoptosis. miR-1269 expression was inversely correlated with RASSF9 expression in GC tissues. RASSF9 was verified to be a direct target of miR-1269 by using a luciferase reporter assay. The overexpression of miR-1269 decreased RASSF9 expression at both the mRNA and protein levels, and the inhibition of miR-1269 increased RASSF9 expression. Importantly, silencing RASSF9 resulted in the same biological effects in GC cells as those induced by overexpression of miR-1269. Overexpression of RASSF9 reversed the effects of miR-1269 overexpression on GC cells. Both miR-1269 overexpression and RASSF9 silencing activated the AKT signaling pathway, which modulated cell cycle regulators (Cyclin D1 and CDK2). In contrast, inhibition of miR-1269 and RASSF9 overexpression inhibited the AKT signaling pathway. Moreover, miR-1269 and RASSF9 also regulated the Bax/Bcl-2 signaling pathway. Conclusions Our results demonstrate that miR-1269 promotes GC cell proliferation and cell cycle G1-S transition by activating the AKT signaling pathway and inhibiting cell apoptosis via regulation of the Bax/Bcl-2 signaling pathway by targeting RASSF9. Our findings indicate an oncogenic role of miR-1269 in GC pathogenesis and the potential use of miR-1269 in GC therapy.

The aim of this research was to detect potential serum biomarkers of melamine diet-induced bladder stones in C57BL/6 mice. Magnetic bead-based weak cationexchange chromatography (MB-WCX) and matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) were employed to detect serum biomarkers in 10 mice fed a melamine diet and 10 control mice. Seventeen peaks (fold change>1.5) with a mass to charge (m/z) value of 1000–10,000 Da were detected in the two groups. Among the significant peaks, five were upregulated and the other 12 were downregulated in the model group. Among the upregulated peaks, 2954.49 and 1710.49 were found to correspond to the peptide regions of NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8(Ndufα8) and basigin, respectively, by liquid chromatography with electrospray ionization and tandem triple quadrupole mass spectrometry(LC-ESI-MS/MS). Western blot analysis was used to detect the expression of Ndufα8 and basigin in another 10 model mice and 10 control mice. The western blot results confirmed the LC-ESI-MS/MS data. The expression of serum basigin and Ndufα8 was partly dependent the concentration of melamine, but no time dependence. In conclusion, Ndufα8 and basigin may be potential serum biomarkers for the detection of melamine diet-induced bladder stones in C57BL/6 mice

Background MicroRNAs play crucial roles in tumorigenesis and tumor progression. miR-770 has been reported to be downregulated in several cancers and affects cancer cell proliferation, apoptosis, metastasis and drug resistance. However, the role and underlying molecular mechanism of miR-770 in human glioma remain unknown and need to be further elucidated. Methods The expression of miR-770 in glioma tissues and cell lines was measured by quantitative real-time PCR (qRT-PCR) to explore the association of miR-770 expression with clinicopathological characteristics. The expression of CDK8 was detected by qRT-PCR and Western blotting in glioma tissues. A target prediction program and a dual-luciferase reporter assay were used to confirm that CDK8 is a target gene of miR-770. MTT and cell counting assays were used to assess the effect of miR-770 on glioma cell proliferation. The cell cycle distribution and apoptosis were examined by flow cytometry. CDK8 siRNA and overexpression were used to further confirm the function of the target gene. Results We demonstrated that miR-770 expression was downregulated in human glioma tissues and cell lines. The overexpression of miR-770 inhibited glioma cell proliferation and cell cycle G1-S transition and induced apoptosis. The inhibition of miR-770 facilitated cell proliferation and G1-S transition and suppressed apoptosis. miR-770 expression was inversely correlated with CDK8 expression in glioma tissues. CDK8 was confirmed to be a direct target of miR-770 by using a luciferase reporter assay. The overexpression of miR-770 decreased CDK8 expression at both the mRNA and protein levels, and the suppression of miR-770 increased CDK8 expression. Importantly, CDK8 silencing recapitulated the cellular and molecular effects observed upon miR-770 overexpression, and CDK8 overexpression eliminated the effects of miR-770 overexpression on glioma cells. Moreover, both exogenous expression of miR-770 and silencing of CDK8 resulted in suppression of the Wnt/β-catenin signaling pathway. Conclusions Our study demonstrates that miR-770 inhibits glioma cell proliferation and G1-S transition and induces apoptosis through suppression of the Wnt/β-catenin signaling pathway by targeting CDK8. These findings suggest that miR-770 plays a significant role in glioma progression and serves as a potential therapeutic target for glioma.

Previous evidence has revealed that long non-coding RNAs serve important functions in numerous types of cancer when dysregulated, including in gastric cancer (GC). In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was used to detect the expression of small integral membrane protein 10 like 2A (linc00086) in GC tissues and non-cancerous tissues, and the expression of linc00086 in GC cell lines was analyzed. A RT-qPCR assay was used to assess linc00086 expression levels in GC cell lines following treatment with 5-Aza-2′-deoxycytidine (5-aza-dC), which is a DNA methyltransferase inhibitor. Small interfering RNA was used to silence the expression of methyl-CpG binding protein 2 (MeCP2), and then the expression of linc00086 was detected. Linc00086 expression was revealed to be downregulated in GC tissues and GC cell lines. Furthermore, it was revealed that 5-aza-dC induced linc00086 expression in SGC-7901 and MKN45 cells, and analysis of CpG methylation by bisulfite sequencing-polymerase chain reaction demonstrated that DNA methylation may regulate the expression of linc00086. MeCP2 is involved in gene regulation by binding to methylated promoters, and it was revealed that the knockdown of the expression of MeCP2 resulted in a higher expression of linc00086. The present study revealed that DNA methylation regulate the expression of linc00086 in human GC cell lines.

A novel palladium–copper catalyzed C(sp3)–C(sp2) bond C–H activation cross-coupling reaction has been developed. A series of 9-aryl-9H-xanthenes and 9,9-diaryl-xanthenes were selectively synthesized in moderate to good yields by controlling the reaction time and temperature.

The serum proteomic profiles of mice exposed to terrified-sound-induced stress and after stress release were in- vestigated. Serum samples from 32 mice were divided into four groups (n=8 each) and analyzed using matrix-assisted laser desorption and ionization time-of-flight mass spectrom- etry techniques (MALDI-TOF MS) combined with magnetic bead-based weak cation-exchange chromatography. ClinProTools software identified several distinct markers that differed between the stressed and control groups and between the stress released and stressed released controls. Of 33m/z peaks that differed among the four groups, 17 were signifi- cantly different (P

Gastric cancer (GC) is one of the most common malignant cancer around the world, however the mechanisms is still unclear. In the present study, we investigated the function of CREB3 regulatory factor (CREBRF) in human GC and explored its relevant molecular mechanism. We found that CREBRF was highly expressed in primary GC tissues and the expression level was associated with the clinicopathologic characteristics of GC. CREBRF silencing inhibited GC cell proliferation and induced G1/G0 to S phase cell cycle arrest through regulating Cyclin A, Cyclin D1 and CDK2 expressions. Furthermore, the results showed that knockdown of CREBRF suppressed the activation of AKT signaling pathway. We further discovered that activating of AKT rescued the effect of CREBRF silencing on cell growth and drove cell re-enter into the S phase of the cell cycle with SC79 (a AKT activator). Taken together, our study demonstrated that CREBRF might promote GC cell proliferation and induce G1-S phase transition through activating AKT signaling pathway. These findings suggest that CREBRF acts as a novel oncogene and may be a potential therapeutic target in therapy of GC.

The pathophysiology of autistic spectrum disorder (ASD) is not fully understood and there are no diagnostic or predictive biomarkers. Glycosylation modified as many as 70% of all human proteins can sensitively reflect various pathological changes. However, little is known about the alterations of glycosylation and glycoproteins in ASD. In this study, serum glycopattern and the maackia amurensis lectin-II binding glycoproteins (MBGs) in 65 children with ASD and 65 age-matched typically developing (TD) children were compared by using lectin microarrays and lectin-magnetic particle conjugate-assisted LC-MS/MS analyses. Expression of Siaα2-3 Gal/GalNAc was significantly increased in pooled (fold change = 3.33, p p = 0.009) serum samples from ASD versus TD children. A total of 194 and 217 MGBs were identified from TD and ASD sera respectively, of which 74 proteins were specially identified or up-regulated in ASD. Bioinformatic analysis revealed abnormal complement cascade and aberrant regulation of response-to-stimulus that might be novel makers or markers for ASD. Moreover, increase of APOD α2-3 sialoglycosylation could sensitively and specifically distinguish ASD samples from TD samples (AUC is 0.88). In conclusion, alteration of MBGs expression and their sialoglycosylation may serve as potential biomarkers for diagnosis of ASD, and provide useful information for investigations into the pathogenesis of ASD.

Gastric cancer (GC) is the second leading cause of cancer-related deaths worldwide, but the mechanisms remain unknown. Here we report that family with sequence similarity 196 member B (FAM196B) is highly expressed in primary GC tissues and the expression level is correlated with the clinicopathologic characteristics of GC. In this experiment, knockdown of FAM196B suppressed GC cell proliferation and induced G1/G0 to S phase cell cycle arrest by regulating Cyclin D1, Cyclin A and CDK2 expressions. Furthermore, we investigated the molecular mechanism of FAM196B action in GC. The results showed that knockdown of FAM196B inhibited the activation of AKT signaling pathway. We further revealed that activating of AKT rescued the effect of FAM196B knockdown on cell proliferation and drove cell re-enter into the S phase of the cell cycle with SC79 (a AKT activator). Our findings demonstrated that FAM196B may promote GC cell proliferation by activating AKT signaling pathway. Taken together, this study provides a new evidence that FAM196B functions as a novel oncogene and could be a potential therapeutic target in therapy of GC.

Aim To reveal the serum proteomic profiling of intraductal carcinoma (IDC) patients in China, establish a serum proteome fractionation technique for choosing magnetic beads for proteomic analysis in breast cancer research; and identify differentially expressed peptides (m/z; P < 0.0001) as potential biomarkers of early IDCs. Methods We used two different kinds of magnetic beads (magnetic bead-based weak cation exchange chromatography (MB-WCX) and immobilized metal ion affinity chromatography (MB-IMAC-Cu)) to analyze 32 patients with early stage (stages I-II) IDC and 32 healthy control serum samples for proteomic profiling by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis. The mass spectra, analyzed using ClinProTools software, distinguished between IDC patients and healthy individuals based on k-nearest neighbor genetic algorithm. Results The serum samples purified in the MB-WCX group provided better proteomic patterns than the MB-IMAC-Cu group. The samples purified by MB-WCX had better average peak numbers, higher peak intensities, and better capturing ability of low abundance proteins or peptides in serum samples. In addition, the MB-WCX and MB-IMAC-Cu purification methods, followed MALDI-TOF MS identification and use of ClinProTools software accurately distinguished patients with early stage IDC from healthy individuals. Conclusion Serum proteomic profiling by MALDI-TOF MS is a novel potential tool for the clinical diagnosis of patients with IDC in China.

A novel and convenient copper-catalyzed oxidative amidation for the synthesis of α-ketoamides has been successfully developed, which uses easily available O-benzoyl hydroxylamines as aminating reagent and oxidant. The reaction proceeds smoothly at room temperature and is compatible with a range of substrates to give the desired products in moderate to good yields.

A series of Pd/SiO 2 and Pd–Ti/SiO 2 catalysts were prepared by the incipient wetness impregnation method. The catalytic performance for selective hydrogenation of acetylene to ethylene was measured under “high concentration acetylene”, “high space velocity” and “no dilution gas” conditions. The crystal structure and particle size of the catalysts were characterized by the X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDS), nitrogen physisorption using the BET method and transmission electron microscope (TEM). The results showed that the titanium oxide in Pd–Ti/SiO 2 catalyst was amorphous and the addition of Ti reduced the particle size of Pd significantly. Comparing to the Pd/SiO 2 catalyst, the ethylene yield increased from 64.1% to 88.3% under Pd–Ti/SiO 2 catalytic system.

A series of shape memory nanocomposites based on diglycidyl ether of bisphenol A (DGEBA) E51/methylhexahydrophthalic anhydride (MHHPA)/multiwalled carbon nanotube (MWCNT) with various stoichiometric ratios (rs) of DGEBA/MHHPA from 0.5 to 1.2 and filler contents of 0.25 and 0.75 wt % are fabricated. Their morphology, curing kinetics, phase transition, mechanical properties, thermal conduction, and shape memory behaviors are systematically investigated. The prepared materials show a wide range of glass transition temperatures (Tg) of ca. 65-140 °C, high flexural modulus (E) at room temperature up to ca. 3.0 GPa, high maximum stress (σm) up to ca. 30 MPa, high strain at break (εb) above 10%, and a fast recovery of 32 s. The results indicate that a small amount of MWCNT fillers (0.75 wt %) can significantly increase all three key mechanical properties (E, σm, and εb) at temperatures close to Tg, the recovery rate, and the repetition stability of the shape memory cycles. All of these remarkable advantages make the materials good candidates for the applications in aerospace and other important fields.

MicroRNA-25 (miR-25) has been reported to be a major miRNA marker in neural cells and is strongly expressed in ischemic brain tissues. However, the precise mechanism and effect of miR-25 in cerebral ischemia/reperfusion (I/R) injury needs further investigations. In the present study, the oxygen-glucose deprivation (OGD) model was constructed in human SH-SY5Y and IMR-32 cells to mimic I/R injury and to evaluate the role of miR-25 in regulating OGD/reperfusion (OGDR)-induced cell apoptosis. We found that miR-25 was downregulated in the OGDR model. Overexpression of miR-25 via miRNA-mimics transfection remarkably inhibited OGDR-induced cell apoptosis. Moreover, Fas was predicted as a target gene of miR-25 through bioinformatic analysis. The interaction between miR-25 and 3'-untranslated region (UTR) of Fas mRNA was confirmed by dual-luciferase reporter assay. Fas protein expression was downregulated by miR-25 overexpression in OGDR model. Subsequently, the small interfering RNA (siRNA)-mediated knockdown of Fas expression also inhibited cell apoptosis induced by OGDR model; in contrast, Fas overexpression abrogated the protective effects of miR-25 on OGDR-induced cells. Taken together, our results indicate that the upregulation of miR-25 inhibits cerebral I/R injury-induced apoptosis through downregulating Fas/FasL, which will provide a promising therapeutic target.

Aberrant expression of microRNAs correlates with the development and progression of human cancers by targeting downstream proteins. MiR-1202 is downregulated in ovarian cancer and clear cell papillary renal cell carcinoma; however, its role in glioma remains unknown. The purpose of this study was to determine the expression and the role of miR-1202 and to elucidate its regulatory mechanism in glioma. We used quantitative real-time polymerase chain reaction to measure miR-1202 expression in both glioma tissues and cell lines. The findings showed that the miR-1202 expression decreased dramatically in clinical glioma tissues and cell lines, and miR-1202 expression was inversely correlated with the expression of Rab1A. Using bioinformatics and luciferase reporter assays, we identified Rab1A as a novel and direct target of miR-1202. In vitro, overexpression of miR-1202 inhibited glioma cell proliferation and induced endoplasmic reticulum stress and apoptosis through targeting Rab1A, whereas suppression of miR-1202 promoted cell proliferation and inhibited endoplasmic reticulum stress and apoptosis. Similarly, silencing Rab1A with small interfering RNA also suppressed glioma cell growth and induced endoplasmic reticulum stress and apoptosis. Taken together, our data indicate that miR-1202 suppresses proliferation and induces endoplasmic reticulum stress and apoptosis through targeting and inhibiting Rab1A in glioma cells. These results suggest miR-1202 as a potential therapeutic target for the treatment of glioma patients.

Metabotropic glutamate receptors (mGluRs) regulate neurogenesis in the mammalian central nervous system during development and throughout adulthood. However, the mechanisms remain unknown. The present study was aimed at investigating the effect of mGluR5 on the differentiation of rat neural progenitor cells (NPCs) into neurons as well as the underlying molecular mechanisms. NPCs were treated with mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), mGluR5 siRNA, and antagonist 6-methyl-2-(phenylethynyl) pyridine hydrochloride (MPEP), respectively. Three different subtypes of neurons (cholinergic, GABAergic, and dopaminergic neurons) were evaluated, and the activation of signaling pathways of mitogen-activated protein kinases was determined. Results showed that CHPG caused rat NPCs to differentiate into neurons, whereas mGluR5 siRNA and MPEP inhibited the cell differentiation. The proportion of cholinergic neurons increased with CHPG treatment and decreased after siRNA or MPEP treatment, whereas there were no significant changes in the proportions of GABAergic and dopaminergic neurons after treatment. The phosphorylated ERK1/2 levels increased after CHPG treatment and decreased after siRNA or MPEP treatment. In conclusion, our findings showed that mGluR5 caused rat NPCs to differentiate into cholinergic neurons by activating ERKs, suggesting that mGluR5 may play a significant role in the mechanism and treatment of degenerative diseases such as Alzheimer's disease.

Aberrant glycogene and glycan expression is intimately associated with carcinogenesis, invasion, and metastasis of gastric cancer (GC); however the regulatory mechanisms for glycogenes in GC cells remain unclear. Methyl-CpG-binding protein 2 (MeCP2) regulates genes by binding to methylated promoters, and in our previous work we found that it is overexpressed in GC cell lines and tissues, functioning as an oncogene. In this study we detected the expression of 212 glycogenes in MeCP2 silenced GC cells versus control using the Agilent Whole Human Genome Microarray and mining the data through bioinformatic analysis. A total of 10 glycogenes exhibited increased expression (FC ≥ 2, P < 0.05), while 16 showed decreased expression (FC ≤ 2, P < 0.05) in the MeCP2 silenced cells, which corresponded to down-regulation of Lewis antigens (UEA-I), T/Tn antigens (PNA), and mature N-glycans (PHA-E and PHA-E+L) and up-regulation of lactosylceramide, a precursor oligosaccharide of N-glycans. Examination of the TCGA Gastric Cancer databases demonstrated that nine glycogenes (24.6%) were oppositely regulated by MeCP2 in MeCP2 knockdown BGC-823 cells relative to their expression level in GC tissues, and might be downstream genes of MeCP2. Individual gene analysis suggested that neutral alpha-glucosidase AB (GANAB) knockdown can rescue the effects of MeCP2 overexpression on GC cells. MeCP2 promotes GANAB by binding to the second methylated CpG island (206 bp, -12916 to -13122) of the GANAB promoter. In conclusion, glycogenes can be either up- or down-regulated by MeCP2 directly or indirectly to alter the glycopatterning and affect the proliferation and apoptosis of GC cells.

The serum proteomic profiles of mice exposed to terrified-sound-induced stress and after stress release were investigated. Serum samples from 32 mice were divided into four groups (n = 8 each) and analyzed using matrix-assisted laser desorption and ionization time-of-flight mass spectrometry techniques (MALDI-TOF MS) combined with magnetic bead-based weak cation-exchange chromatography. ClinProTools software identified several distinct markers that differed between the stressed and control groups and between the stress released and stressed released controls. Of 33 m/z peaks that differed among the four groups, 17 were significantly different (P

In this study, we investigated the effects of metabotropic glutamate receptor 5 (mGluR5) on NSC proliferation under hypoxia by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, diameter measurement of neurospheres, bromodeoxyuridine (BrdU) incorporation assay and cell cycle analysis. The cell death of NSCs was evaluated by terminal dUTP nickend labeling (TUNEL) assay and Hoechst staining. The expression of cyclin D1 and the activation of mitogenactivated protein kinases (MAPKs) signaling pathway were analyzed by immunoblotting assay. Results The results showed that hypoxia promoted the mGluR5 expression on NSCs. Under hypoxia, mGluR5 agonist DHPG and CHPG significantly increased NSC proliferation in cell activity, diameter of neurospheres, bromodeoxyuridine (BrdU) incorporation and cell division, and expression of cyclin D1 with decreasing of cell death. mGluR5 siRNA and antagonist MPEP decreased the NSC proliferation and expression of cyclin D1 with increasing of cell death. Phosphorylated JNK and ERK increased with the proliferation of NSCs after mGluR5 agonist DHPG and CHPG treatment under hypoxia, while p-p38 level decreased. Conclusions These results demonstrated that the expression of mGluR5 was upregulated during the proliferation of NSCs stimulated by hypoxia in vitro. The activation of ERK and JNK signaling pathway and the expression of cyclin D1 were increased in the process. These finding suggesting the involvement of mGluR5 in NSC proliferation and providing a target molecule in neural repair after ischemia/hypoxia injury of CNS.