Anti-DR5 mAb Ameliorate Adjuvant Arthritis Rats Through Inducing Synovial Cells Apoptosis

Objective: Study the therapeutic effects and immunoregulatory mechanisms of anti-DR5 mAb on adjuvant arthritis (AA) rats. Methods: AA rats induced by CFA, were treated with anti-DR5 mAb through mainline administration. Effect on the synovial membranes of the tissues was detected by H&E staining. Flow cytometry and MTT assay were used for detecting the induced apoptosis in an in vitro system and TUNEL assay was used for analysis in an in vivo system. The involvement of the apoptotic pathway was further proved by a caspase inhibition assay. Results: Anti-DR5 mAb could induce synovial cell apoptosis in an in vitro system, which was related with the mRNA expression of DR5 on the cell surface. The mRNA expressions of c-myc and bcl-2 were decreased in synovial cells and those of p21, p53, and bax were increased. The protein expressions of caspase-8/3/9, RANKL, JNK2, and c-Jun were raised and that of bcl-2 was decreased. When the caspase inhibitor was added to the synovial cells treated with anti-DR5 mAb, it showed a dose-dependence inhibition effect, indicating that anti-DR5 mAb inducing apoptosis might be through the caspase pathway. Conclusion: This study shows that anti-DR5 mAb can ameliorate arthritic symptoms. The mechanisms of the treatment are related to the increase in synovial cell apoptosis by regulating the mRNA expression of DR5 and apoptosis-related genes, prolonging the duration of the cell cycle by modulation of the mRNA expression of cell cycle-related genes, and the protein expression of the molecules in the caspase pathway and RANKL, JNK2, and c-Jun. Exp Biol Med 234:1468-1476, 2009Scientific Research Foundation of Fujian Province [2007J0116

Pd/ZnO catalysts with different origins for high chemoselectivity in acetylene semi-hydrogenation

The heterogeneity of active sites is the main obstacle for selectivity control in heterogeneous catalysis. Single atom catalysts (SACS) with homogeneous isolated active sites are highly desired in chemoselective transformations. In this work, a Pd-1/ZnO catalyst with single-atom dispersion of Pd active sites was achieved by decreasing the Pd loading and reducing the sample at a relatively low temperature. The Pd-1/ZnO SAC exhibited excellent catalytic performance in the chemoselective hydrogenation of acetylene with comparable chemoselectivity to that of PdZn intermetallic catalysts and a greatly enhanced utilization of Pd metal. Such unusual behaviors of the Pd-1/ZnO SAC in acetylene semi-hydrogenation were ascribed to the high-valent single Pd active sites, which could promote electrostatic interactions with acetylene but restrain undesired ethylene hydrogenation via the spatial restrictions of o-chemical bonding toward ethylene. (C) 2016, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved

Opposite effective connectivity in the posterior cingulate and medial prefrontal cortex between first-episode schizophrenic patients with suicide risk and healthy controls.

OBJECTIVE: The schizophrenic patients with high suicide risk are characterized by depression, better cognitive function, and prominent positive symptoms. However, the neurobiological basis of suicide attempts in schizophrenia is not clear. The suicide in schizophrenia is implicated in the defects in emotional process and decision-making, which are associated with prefrontal-cingulate circuit. In order to explore the possible neurobiological basis of suicide in schizophrenia, we investigated the correlation of prefrontal-cingulate circuit with suicide risk in schizophrenia via dynamic casual modelling. METHOD: Participants were 33 first-episode schizophrenic patients comprising of a high suicide risk group (N = 14) and a low suicide risk group (N = 19). A comparison group of healthy controls (N = 15) were matched for age, gender and education. N-back tasking functional magnetic resonance imaging data was collected. RESULTS: Compared with healthy controls group, the two patients groups showed decreased task-related suppression during 2-back task state versus baseline state in the left posterior cingulate and medial prefrontal cortex; the hyper-connectivity from the left posterior cingulate cortex to the left medial prefrontal cortex existed in both schizophrenic patients groups, but hypo-connectivity in the opposite direction only existed in the schizophrenic patients group with high suicide risk. CONCLUSIONS: The hyper-connectivity from the left posterior cingulate cortex to the left medial prefrontal cortex may suggest that the abnormal effective connectivity was associated with risk for schizophrenia. The hypo-connectivity in the opposite direction may represent a possible correlate of increased vulnerability to suicide attempt

PdZn Intermetallic Nanostructure with Pd–Zn–Pd Ensembles for Highly Active and Chemoselective Semi-Hydrogenation of Acetylene

Intermetallic alloying of one active metal to another inert metal provides not only the improved dispersion of active centers but also a unique and homogeneous ensemble of active sites, thus offering new opportunities in a variety of reactions. Herein, we report that PdZn intermetallic nanostructure with Pd–Zn–Pd ensembles are both highly active and selective for the semihydrogenation of acetylene to ethylene, which is usually inaccessible due to the sequential hydrogenation to ethane. Microcalorimetric measurements and density functional theory calculations demonstrate that the appropriate spatial arrangement of Pd sites in the Pd–Zn–Pd ensembles of the PdZn alloy leads to the moderate σ-bonding mode for acetylene with two neighboring Pd sites while the weak π-bonding pattern of ethylene adsorption on the single Pd site, which facilitates the chemisorption toward acetylene and promotes the desorption of ethylene from the catalyst surface. As a result, it leads to the kinetic favor of the selective conversion of acetylene to ethylene

Mitochondria-Directed Fluorescent Probe for the Detection of Hydrogen Peroxide near Mitochondrial DNA

It is important to detect hydrogen peroxide (H₂O₂) near mitochondrial DNA (mtDNA) because mtDNA is more prone to oxidative attack than nuclear DNA (nDNA). In this study, a mitochondria-targeted fluorescence probe, <b>pep3-NP1</b>, has been designed and synthesized. The probe contains a DNA-binding peptide, a H₂O₂ fluorescence reporter, and a positively charged red emissive styryl dye to facilitate accumulation in mitochondria. Due to groove binding of the peptide with DNA, the styryl dye of <b>pep3-NP1</b> intercalated into the bases of DNA, leading to an increase in red fluorescence intensity (centered at 646 nm) and quantum yield. In this case, <b>pep3-NP1</b> was a turn-on probe for labeling DNA. Subcellular locations of <b>pep3-NP1</b> and MitoTracker suggested that <b>pep3-NP1</b> mostly accumulated in the mitochondria of live cells. Namely, as an intracellular DNA marker, <b>pep3-NP1</b> bound to mtDNA. In the presence of H₂O₂, <b>pep3-NP1</b> emitted green fluorescence (centered at 555 nm). Thus, the ratio of green with red fluorescence of <b>pep3-NP1</b> was suitable to reflect the change of the H₂O₂ level near mtDNA in living cells. The detecting limit for H₂O₂ was estimated at 2.9 and 5.0 μM in vitro and in cultured cells, respectively. The development of <b>pep3-NP1</b> could help in studies to protect mtDNA from oxidative stress

A Highly Sensitive Ratiometric Fluorescent Probe for the Detection of Cytoplasmic and Nuclear Hydrogen Peroxide

As a marker for oxidative stress and a second messenger in signal transduction, hydrogen peroxide (H₂O₂) plays an important role in living systems. It is thus critical to monitor the changes in H₂O₂ in cells and tissues. Here, we developed a highly sensitive and versatile ratiometric H₂O₂ fluorescent probe (<b>NP1</b>) based on 1,8-naphthalimide and boric acid ester. In response to H₂O₂, the ratio of its fluorescent intensities at 555 and 403 nm changed 1020-fold within 200 min. The detecting limit of <b>NP1</b> toward H₂O₂ is estimated as 0.17 μM. It was capable of imaging endogenous H₂O₂ generated in live RAW 264.7 macrophages as a cellular inflammation response, and especially, it was able to detect H₂O₂ produced as a signaling molecule in A431 human epidermoid carcinoma cells through stimulation by epidermal growth factor. This probe contains an azide group and thus has the potential to be linked to various molecules via the click reaction. After binding to a Nuclear Localization Signal peptide, the peptide-based combination probe (<b>pep-NP1</b>) was successfully targeted to nuclei and was capable of ratiometrically detecting nuclear H₂O₂ in living cells. These results indicated that <b>NP1</b> was a highly sensitive ratiometric H₂O₂ dye with promising biological applications

Five hypothesized dynamic casual models during 2-back task.

<p>Each model includes the left medial prefrontal cortex (MPFC) and the ipsilateral posterior cingulate cortex (PCC), in which the arrows indicate extrinsic stimulation and functional connections direction. M1, M2 and M3 comprised bi-directional connections with respectively driving input into PCC or MPFC or both of the regions. M4 only contained unidirectional connection from the PCC to MPFC with driving input into PCC and M5 was completely opposite to M4. M1, M4 and M2 were identified as the optimal models in HSR, LSR and HC respectively. HSR: schizophrenic patients with high suicide risk; LSR: schizophrenic patients with low suicide risk; HC: healthy controls.</p

Regions with significant activations at rest state compared with 2-back task (<i>p</i><0.05, FWE corrected).

<p>Regions with significant activations at rest state compared with 2-back task (<i>p</i><0.05, FWE corrected).</p