Design and synthesis of iso-allo-DNJ and L-isoDALDP derivatives: pursuit of potent and selective inhibitors of α-glucosidase.

A series of iso-allo-DNJ and L-isoDALDP derivatives were synthesized from dithioacetal 16 with sequential and highly diastereoselective Ho and Henry reactions, and aziridinium intermediate-mediated ring rearrangement as key steps. Glycosidase inhibition assay found four of them as selective α-glucosidase inhibitors, and the less substituted compound 30 showed more potent α-glucosidase inhibition (IC50 = 9.3 µM) than the others. Molecular docking study revealed different docking modes of the iso-allo-DNJ and L-isoDALDP derivatives from their parent compounds, and also the similarity of compound 30 to isofagomine.

Synthesis and glycosidase inhibition of N-substituted derivatives of 1,4-dideoxy-1,4-imino-d-mannitol (DIM).

N-Substituted derivatives of 1,4-dideoxy-1,4-imino-d-mannitol (DIM), the pyrrolidine core of swainsonine, have been synthesized efficiently and stereoselectively from d-mannose with 2,3:5,6-di-O-isopropylidene DIM (10) as a key intermediate. These N-substituted derivatives include N-alkylated, N-alkenylated, N-hydroxyalkylated and N-aralkylated DIMs with the carbon number of the alkyl chain ranging from one to nine. The obtained 33 N-substituted DIM derivatives were assayed against various glycosidases, which allowed a systematic evaluation of their glycosidase inhibition profiles. Though N-substitution of DIM decreased their α-mannosidase inhibitory activities, some of the derivatives showed significant inhibition of other glycosidases.

Genome-Wide Identification and Transcriptomic Analysis of MicroRNAs Across Various Amphioxus Organs Using Deep Sequencing.

Amphioxus is the closest living invertebrate proxy of the vertebrate ancestor. Systematic gene identification and expression profile analysis of amphioxus organs are thus important for clarifying the molecular mechanisms of organ function formation and further understanding the evolutionary origin of organs and genes in vertebrates. The precise regulation of microRNAs (miRNAs) is crucial for the functional specification and differentiation of organs. In particular, those miRNAs that are expressed specifically in organs (OSMs) play key roles in organ identity, differentiation, and function. In this study, the genome-wide miRNA transcriptome was analyzed in eight organs of adult amphioxus Branchiostoma belcheri using deep sequencing. A total of 167 known miRNAs and 23 novel miRNAs (named novel_mir), including 139 conserved miRNAs, were discovered, and 79 of these were identified as OSMs. Additionally, analyses of the expression patterns of eight randomly selected known miRNAs demonstrated the accuracy of the miRNA deep sequencing that was used in this study. Furthermore, potentially OSM-regulated genes were predicted for each organ type. Functional enrichment of these predicted targets, as well as further functional analyses of known OSMs, was conducted. We found that the OSMs were potentially to be involved in organ-specific functions, such as epidermis development, gonad development, muscle cell development, proteolysis, lipid metabolism, and generation of neurons. Moreover, OSMs with non-organ-specific functions were detected and primarily include those related to innate immunity and response to stimuli. These findings provide insights into the regulatory roles of OSMs in various amphioxus organs.

Design and synthesis of functionalized coordination polymers as recyclable heterogeneous photocatalysts.

The functionalized ligand 9,10-anthraquinone-1,4-dicarboxylate acid (H2AQDC) was designed and synthesized in order to develop metal-organic coordination polymers as heterogeneous catalysts with a photosensitizing feature. Two major considerations of the ligand design are anthraquinone moieties for photosensitizing to harvest light and carboxylate groups for polymeric coordination toward less solubility. A series of transition metal complexes based on this ligand were synthesized subsequently, namely {Co(AQDC)(H2O)3·2H2O}n (Co-AQDC), {Ni(AQDC)(H2O)3·2H2O}n (Ni-AQDC), {[Cu(AQDC)(H2O)3][Cu(AQDC)(H2O)2(DMF)]·(H2O)4}n (Cu-AQDC), {Zn1.5(AQDC)(OH)(H2O)2·H2O}n (Zn-AQDC), {Ag2(AQDC)(CH3OH)}n (Ag-AQDC). Both the ligand and its transition metal complexes are able to catalyze the visible-light driven oxidation reactions of alkynes into 1,2-diketones in air under mild conditions, in which compound Ni-AQDC demonstrates the best activity. This catalyst can be easily isolated from the reaction mixture by filtration with a trace amount of loss in solution and is ready for recycled use after simple washing and drying without any need for regeneration. Remarkably, the catalyst shows no loss of activity after five catalytic cycles and X-ray powder diffraction proves no change in the structure after five runs. This designed metal-organic coordination polymer represents an environmentally friendly, economical and recyclable photocatalyst, constituting a good candidate for photocatalytic organic syntheses in terms of green chemistry.

Diagnostic accuracy of myocardial magnetic resonance perfusion to diagnose ischemic stenosis with fractional flow reserve as reference: systematic review and meta-analysis.

OBJECTIVES: This paper systematically analyzed the performance of magnetic resonance (MR) perfusion to diagnose coronary artery disease (CAD) with fractional flow reserve (FFR) as the reference standard. BACKGROUND: Myocardial MR perfusion has passed the stage of a research technique and has demonstrated the ability to detect functional or ischemic stenosis of coronary arteries. However, the evidence is limited to single-center studies and small sample sizes. METHODS: We searched PubMed and Embase databases for all published studies that evaluated the accuracy of MR perfusion to diagnose CAD versus FFR. We used an exact binomial rendition of the bivariate mixed-effects regression model with test type as a random-effects covariate to synthesize the available data. Based on Bayes' theorem, the post-test probability was calculated to guide MR perfusion's clinical utility. RESULTS: We identified 14 studies evaluating 1,073 arteries and 650 patients. The pooled sensitivity and specificity were 0.90 (95% confidence interval [CI]: 0.86 to 0.93) and 0.87 (95% CI: 0.82 to 0.90) at the patient level and 0.89 (95% CI: 0.83 to 0.92) and 0.86 (95% CI: 0.77 to 0.92) at the artery and territory levels, respectively. The area under the summary receiver-operating characteristic at the patient level was 0.95 (95% CI: 0.92 to 0.96) and 0.93 (95% CI: 0.91 to 0.95) at the artery and territory levels, respectively. MR perfusion could increase the post-test probability of CAD >80% in patients with a pre-test probability of >37% and can decrease post-test probability of CAD <20% with a pre-test probability of <72%. CONCLUSIONS: With FFR as the reference standard, the diagnostic ability of MR perfusion to detect ischemic CAD is high.

SPECT myocardial perfusion versus fractional flow reserve for evaluation of functional ischemia: a meta analysis.

PURPOSE: The present meta-analysis illustrates the accuracy of myocardial perfusion SPECT (MPS) to diagnose functional stenotic coronary artery disease (CAD) with fractional flow reserve (FFR) as standard reference. METHODS: All investigators screened and selected studies that compared MPS with FFR in symptomatic patients with suspected CAD. Patients and study characteristics were independently extracted by two investigators; differences were resolved by consensus. RESULTS: 13 articles, including 1,017 patients, 699 vessels were included in the study. No significant publication bias was detected (P=0.65). At the patient level, the summary sensitivity and specificity were 77% (95% confidence interval [CI], 70-83%) and 77% (95%CI, 67-84%) for MPS. Vessel-level pooled sensitivity was 66% (95%CI, 57-74%) and specificity was 81% (95%CI, 70-89%). The overall diagnostic performance of MPS was moderate. [The area under the summary receiver operating characteristic (sROC) curve was 0.83]. No study influenced the pooled results larger than 0.03. CONCLUSIONS: The accuracy between FFR and MPS SPECT was moderate.

[Osteoid osteoma of the mandibular condyle: report of one case].

Osteoid Osteoma is rare in mandibular condyle. A case of osteoid osteoma in the condyle was reported in this paper. The clinical manifestation, radiographic characteristic, pathologic diagnosis were discussed. Nidus is the key in diagnosing osteoid osteoma, and the final diagnosis is based on pathological findings.