5-(4-Fluoro­phen­yl)-2-furylmethyl N-(2,6-difluoro­benzo­yl)carbamate

The title compound, C19H12F3NO4, was synthesized by the reaction of 5-(4-fluoro­phen­yl)-2-furan­methanol and 2,6-difluoro­benzoyl­isocyanate. The seven atoms of the fluorophenyl group are disordered over two positions with site occupancy factors ca 0.6 and 0.4. The dihedral angle between the furan and fluorophenyl rings is 1.58°. In the crystal structure, the mol­ecules are linked via inter­molecular N—H⋯O hydrogen bonds to form chains

N′-tert-Butyl-5-(4-chloro­phen­yl)furan-2-carbohydrazide

In the title mol­ecule, C15H17ClN2O2, the furan and benzene rings form a dihedral angle of 15.35 (8)°. In the crystal structure, inter­molecular N—H⋯O hydrogen bonds link the mol­ecules into chains extended in the [010] direction

Molecular identification of Trichinella spiralis nudix hydrolase and its induced protective immunity against trichinellosis in BALB/c mice

Background: Nudix hydrolases (Nd) is a widespread superfamily, which is found in all classes of organism, hydrolyse a wide range of organic pyrophosphates and has a ‘housecleaning’ function. The previous study showed that Trichinella spiralis Nd (TsNd) bound to intestinal epithelial cells (IECs), and the vaccination of mice with T7 phage-displayed TsNd polypeptides produced protective immunity. The aim of this study was to clone, express and identify the full-length TsNd and to investigate its immune protection against T. spiralis infection. Methods: The full-length cDNA sequence of TsNd gene encoding a 46 kDa protein from T. spiralis intestinal infective larvae (IIL) was cloned and identified. The antigenicity of rTsNd was analyzed by Western blot. Transcription and expression of TsNd at T. spiralis different stages were observed by RT-PCR and IFT. The levels of the specific total IgG, IgG1 and IgG2a antibodies to rTsNd were determined by ELISA. The immune protection of rTsNd against T. spiralis infection was investigated. Results: Sequence and phylogenetic analysis revealed that TsNd had a nudix motif located at 226-244aa, which had high homology and the closest evolutionary status with T. pseudospiralis. The rTsNd was obtained after expression and purification. Western blot analysis showed that anti-rTsNd serum recognized the native TsNd protein in crude antigens of muscle larvae (ML), IIL, adult worms (AW) and newborn larvae (NBL), and ES antigens of ML. Transcription and expression of TsNd gene was observed in all developmental stages of T. spiralis (ML, IIL, AW and NBL), with high level expression in IIL. An immunolocalization analysis identified TsNd in the cuticle, stichocytes and reproductive organs of the parasite. Following immunization, anti-rTsNd IgG levels were increased, and the levels of IgG1 were more significantly higher than that of IgG2a. After a challenge infection with T. spiralis, mice immunized with the rTsNd displayed a 57.7% reduction in adult worms and a 56.9% reduction in muscle larval burden. Conclusions: TsNd induced a partial protective immunity in mice and could be considered as a novel candidate vaccine antigen against trichinellosis

Association Between Connectivity of Hippocampal Sub-Regions and Auditory Verbal Hallucinations in Schizophrenia

Background: Hippocampal dysconnectivity has been detected in schizophrenia patients with auditory verbal hallucinations (AVHs). Neuroanatomical evidence has indicated distinct sub-regions in the hippocampus, but which sub-regions within the hippocampus may emerge dysfunction in the brain network, and the relationship between connection strength and the severity of this debilitating disorder have yet to be revealed. Masked independent component analysis (mICA), i.e., ICA restricted to a defined region of interest, can provide insight into observing local functional connectivity in a particular brain region. We aim to map out the sub-regions in the hippocampus with dysconnectivity linked to AVHs in schizophrenia.Methods: In this functional magnetic resonance imaging study of schizophrenia patients with (n = 57) and without (n = 83) AVHs, and 71 healthy controls, we first examined hippocampal connectivity using mICA, and then the correlation between connection metric and clinical severity was generated.Results: As compared with patients without AVHs, mICA showed a group of hyper-connections for the left middle part, as well as another group of hypo-connections for the bilateral antero-lateral and right antero-medial parts in patients with AVHs. Connectivity was linked to the clinical symptoms scores in the sample of patients with AVHs.Conclusion: These findings demonstrate that the left middle part is more densely connected, but the bilateral antero-lateral and right antero-medial parts are more sparsely connected in schizophrenia patients with AVHs. The findings in the present study show proof of precious location in the hippocampus mediating the neural mechanism behind AVHs in schizophrenia

R-848 triggers the expression of TLR7/8 and suppresses HIV replication in monocytes

<p>Abstract</p> <p>Background</p> <p>Toll-like receptors (TLR) 7 and 8 are important in single-stranded viral RNA recognition and may play a role in HIV infection and disease progression. We analyzed TLR7/8 expression and signaling in monocytes from HIV-infected and uninfected subjects to investigate a pathway with new potential for the suppression of HIV replication.</p> <p>Methods</p> <p>Eighty-one HIV-infected and uninfected subjects from Liaoning and Henan provinces in China participated in this study. Monocytes were isolated from subjects' peripheral blood mononuclear cells by magnetic bead selection. TLR7 and TLR8 mRNA was measured using quantitative real-time reverse transcriptase PCR. R-848 (resiquimod) was used as a ligand for TLR7 and TLR8 in order to 1) assess TLR7/8-mediated monocyte responsiveness as indicated by IL-12 p40 and TNF-α secretion and 2) to examine HIV replication in cultured monocytes in the presence of R-848.</p> <p>Results</p> <p>We found that expression of TLR7/8 mRNA in peripheral blood monocytes decreased with disease progression. TLR7 expression was decreased with stimulation with the TLR7/8 agonist, R-848, in vitro, whereas TLR8 expression was unaffected. Following R-848 stimulation, monocytes from HIV-infected subjects produced significantly less TNF-α than those from uninfected subjects, but trended towards greater production of IL-12 than stimulated monocytes from uninfected subjects. R-848 stimulation also suppressed HIV replication in cultured monocytes.</p> <p>Conclusions</p> <p>Our study provides evidence that the TLR7 and TLR8 triggering can suppress HIV replication in monocytes and lead to postpone HIV disease progression, thereby offering novel targets for immunomodulatory therapy.</p

Peking University Health Science Center Model of Clinical Pharmacy Education and Clinical Pharmacist Services

In the 1950s, clinical pharmacy emerged in the United States and gradually developed into an indispensable component of the clinical services system. The American College of Clinical Pharmacy defines clinical pharmacy as a pharmaceutical field that focuses on the science and practice of rational drug use. Since its emergence, people have explored the clinical drug management needs that can be provided by pharmacists. Initially, as a supplement to nurses, pharmacists worked in clinical settings and were mainly involved in reducing medication errors, controlling drug costs, and monitoring adverse reactions. The working model and laws and regulations regarding pharmacists had thus been explored and established at that time, but their position was not yet formally defined. In the 1970s and 1980s, a working model of clinical pharmacists became gradually established through the publication of clinical pharmacy guidelines and improvements to the evaluation system. In the 1990s, the focus of clinical pharmacy turned from drugs to patients; being patient-centered, clinical pharmacists reduced adverse reactions, decreased mortality, and improved treatment effectiveness, thus replacing some of internists&apos; work.SCI(E)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)[email protected]

Heterogeneous Environment Aware Streaming Graph Partitioning

With the increasing availability of graph data and widely adopted cloud computing paradigm, graph partitioning has become an efficient pre-processing technique to balance the computing workload and cope with the large scale of input data. Since the cost of partitioning the entire graph is strictly prohibitive, there are some recent tentative works towards streaming graph partitioning which run faster, are easily parallelized, and can be incrementally updated. Most of the existing works on streaming partitioning assume that worker nodes within a cluster are homogeneous in nature. Unfortunately, this assumption does not always hold. Experiments show that these homogeneous algorithms suffer a significant performance degradation when running at heterogeneous environment. In this paper, we propose a novel adaptive streaming graph partitioning approach to cope with heterogeneous environment. We first formally model the heterogeneous computing environment with the consideration of the unbalance of computing ability (e.g., the CPU frequency) and communication ability (e.g., the network bandwidth) for each node. Based on this model, we propose a new graph partitioning objective function that aims to minimize the total execution time of the graph-processing job. We then explore some simple yet effective streaming algorithms for this objective function that can achieve balanced and efficient partitioning result. Extensive experiments are conducted on a moderate sized computing cluster with real-world web and social network graphs. The results demonstrate that the proposed approach achieves significant improvement compared with the state-of-the-art solutions