One-Pot Synthesis of Acetylacetonate-Based Isomeric Phosphorescent Cyclometalated Iridium(III) Complexes via Random Cyclometalation: A Strategy for Excited-State Manipulation.

The excited-state manipulation of the phosphorescent iridium(III) complexes plays a vital role in their photofunctional applications. The development of the molecular design strategy promotes the creative findings of novel iridium(III) complexes. The current molecular design strategies for iridium(III) complexes mainly depend on the selective cyclometalation of the ligands with the iridium(III) ion, which is governed by the steric hindrance of the ligand during the cyclometalation. Herein, a new molecular design strategy (i.e., random cyclometalation strategy) is proposed for the effective excited-state manipulation of phosphorescent cyclometalated iridium(III) complexes. Two series of new and separable methoxyl-functionalized isomeric iridium(III) complexes are accessed by a one-pot synthesis via random cyclometalation, resulting in a dramatic tuning of the phosphorescence peak wavelength (∼57 nm) and electrochemical properties attributed to the high sensitivity of their excited states to the position of the methoxyl group. These iridium(III) complexes show intense phosphorescence ranging from the yellow (567 nm) to the deep-red (634 nm) color with high photoluminescence quantum yields of up to 0.99. Two deep-red emissive iridium(III) complexes with short decay lifetimes are further utilized as triplet emitters to afford efficient solution-processed electroluminescence with reduced efficiency roll-offs.

Estrogen-induced circRNA, circPGR, functions as a ceRNA to promote estrogen receptor-positive breast cancer cell growth by regulating cell cycle-related genes.

Estrogen and estrogen receptor (ER)-regulated gene transcriptional events have been well known to be involved in ER-positive breast carcinogenesis. Meanwhile, circular RNAs (circRNAs) are emerging as a new family of functional non-coding RNAs (ncRNAs) with implications in a variety of pathological processes, such as cancer. However, the estrogen-regulated circRNA program and the function of such program remain uncharacterized. Methods: CircRNA sequencing (circRNA-seq) was performed to identify circRNAs induced by estrogen, and cell proliferation, colony formation, wound healing, transwell and tumor xenograft experiments were applied to examine the function of estrogen-induced circRNA, circPGR. RNA sequencing (RNA-seq) and ceRNA network analysis wereperformed to identify circPGR's target genes and the microRNA (miRNA) bound to circPGR. Anti-sense oligonucleotide (ASO) was used to assess circPGR's effects on ER-positive breast cancer cell growth. Results: Genome-wide circRNA profiling by circRNA sequencing (circRNA-seq) revealed that a large number of circRNAs were induced by estrogen, and further functional screening for the several circRNAs originated from PGR revealed that one of them, which we named as circPGR, was required for ER-positive breast cancer cell growth and tumorigenesis. CircPGR was found to be localized in the cytosol of cells and functioned as a competing endogenous RNA (ceRNA) to sponge miR-301a-5p to regulate the expression of multiple cell cycle genes. The clinical relevance of circPGR was underscored by its high and specific expression in ER-positive breast cancer cell lines and clinical breast cancer tissue samples. Accordingly, anti-sense oligonucleotide (ASO) targeting circPGR was proven to be effective in suppressing ER-positive breast cancer cell growth. Conclusions: These findings reveled that, besides the well-known messenger RNA (mRNA), microRNA (miRNA), long non-coding RNA (lncRNA) and enhancer RNA (eRNA) programs, estrogen also induced a circRNA program, and exemplified by circPGR, these estrogen-induced circRNAs were required for ER-positive breast cancer cell growth, providing a new class of therapeutic targets for ER-positive breast cancer.

Comparative efficacy and safety of multiple antiplatelet therapies for secondary prevention of ischemic stroke or transient ischemic attack: A network meta-analysis.

BACKGROUND: Antiplatelet therapies for secondary prevention of ischemic stroke or transient ischemic attack (TIA) is a highly active research topic with five critical drugs obtained by visual analysis. We aimed to compare and rank multiple antiplatelet therapies using a network meta-analysis. METHODS: Relevant medical databases were searched. Eligible randomized controlled trials (RCTs) which examined any comparisons involving mono- or dual antiplatelet therapies, based on aspirin, clopidogrel, dipyridamole, ticlopidine, cilostazol and placebo for patients with noncardioembolic ischemic stroke or TIA, were included. 14 outcomes were assessed. Primary outcomes were stroke recurrence, composite events (stroke recurrence, myocardial infarction and vascular death), and intracranial hemorrhage. PROSPERO registered number CRD42017069728. RESULTS: 45 RCTs with 173,131 patients were included in network meta-analysis, involving eight antiplatelet therapies. Cilostazol and clopidogrel were statistically more efficacious than aspirin (odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.47-0.88; OR = 0.77, 95%CI = 0.62-0.95) and dipyridamole (OR = 0.64, 95%CI = 0.44-0.93; OR = 0.76, 95%CI = 0.58-0.99) in reducing stroke recurrence, and showed significant benefits in reducing composite events compared with aspirin (OR = 0.63, 95%CI = 0.45-0.89; OR = 0.90, 95%CI = 0.83-0.97). No significant difference was found between cilostazol and clopidogrel in intracranial hemorrhage. Weighted regression suggested cilostazol was hierarchically the optimum treatment in consideration of both efficacy and safety, followed by clopidogrel. CONCLUSION: Cilostazol and clopidogrel are probably promising options for secondary prevention of ischemic stroke or TIA. Both of them reduce stroke recurrence similarly compared with aspirin or dipyridamole, and reduce composite events compared with aspirin. Further studies are needed to confirm this finding.

[Biodiversity and Function Analyses of BIOLAK Activated Sludge Metagenome].

The BIOLAK is a multi-stage activated sludge process, which has been successfully promoted worldwide. However, the biological community and function of the BIOLAK activated sludge ( the core component in the process) have not been reported so far. In this study, taking Lianyungang Dapu Industrial Zone WWTP as an example, a large-scale metagenomic data (428 588 high-quality DNA sequences) of the BIOLAK activated sludge were obtained by means of a new generation of high-throughput sequencing technology. Amazing biodiversity was revealed in the BIOLAK activated sludge, which included 47 phyla, 872 genera and 1351 species. There were 33 phyla identified in the Bacteria domain (289 933 sequences). Proteohacteria was the most abundant phylum (62.54%), followed by Bacteroidetes (11.29%), Nitrospirae ( 5. 65%) and Planctomycetes (4.79%), suggesting that these groups played a key role in the BIOLAK wastewater treatment system. Among the 748 bacterial genera, Nitrospira (5.60%) was the most prevalent genus, which was a key group in the nitrogen cycle. Followed by Gemmatimonas (2.45%), which was an important genus in the biological phosphorus removal process. In Archaea domain (1019 sequences), three phyla and 39 genera were detected. In Eukaryota domain (1055 sequences), 60 genera and 10 phyla were identified, among which Ciliophora was the largest phylum (257 sequences). Meanwhile, 448 viral sequences were detected in the BIOLAK sludge metagenome, which were dominated by bacteriophages. The proportions of nitrogen, aromatic compounds and phosphorus metabolism in the BIOLAK sludge were 2.50%, 2.28% and 1.56%, respectively, which were higher than those in the sludge of United States and Australia. Among four processes of nitrogen metabolism, denitrification-related genes were most abundant (80.81%), followed by ammonification (12.78%), nitrification,(4.38%) and nitrogen fixation (2.04%). In conclusion, the BIOLAK activated sludge had amazing biodiversity, meanwhile, functional genes involved in nitrogen, aromatic compounds and phosphorus metabolism were very abundant.

The first mitochondrial genome from Mysida (Crustacea: Malacostraca) reveals an unusual gene arrangement.

This is the first report to present the Neomysis orientalis mitochondrial genome as a representative from the order Mysida. While mitochondrial protein-coding genes (PCGs) commonly use several alternatives to ATN as start codons, all 13 PCGs in N. orientalis mitochondrial genome initiate with ATG or ATA. Five PCGs (atp6. atp8. cob. nad4 and nad4L) start with ATG, while the other genes (cox1-3. nad1-3. nad5 and nad6) start with ATA. Only two PCGs (cox2 and nad2) in the N. orientalis mitochondrial genome end with incomplete stop codons (T- or TA-), and all the remaining ones have TAA or TAG stop codon. Only one PCG (nad4L) is encoded on the light strand and all other 12 PCGs are located at the heavy strand. Both rRNAs (srRNA and lrRNA) are encoded on the light strand. In common with 15 of the other 18 mitochondrial genomes from Peracarida, the major gene arrangement in the N. orientalis mitochondrial genome is different from the pancrustacean ground pattern. The largest conserved gene block in N. orientalis only contains two genes but those in the other 18 peracarid mitochondrial genomes contain more than five genes. Thus, the N. orientalis mitochondrial genome, as the first mitochondrial genome from the order Mysida, reveals an unusual gene arrangement that is unique compared with the other malacostracan mitochondrial genomes.

Adaptive evolution of cry genes in Bacillus thuringiensis: implications for their specificity determination.

The cry gene family, produced during the late exponential phase of growth in Bacillus thuringiensis, is a large, still-growing family of homologous genes, in which each gene encodes a protein with strong specific activity against only one or a few insect species. Extensive studies are mostly focusing on the structural and functional relationships of Cry proteins, and have revealed several residues or domains that are important for the target recognition and receptor attachment. In this study, we have employed a maximum likelihood method to detect evidence of adaptive evolution in Cry proteins, and have identified 24 positively selected residues, which are all located in Domain II or III. Combined with known data from mutagenesis studies, the majority of these residues, at the molecular level, contribute much to the insect specificity determination. We postulate that the potential pressures driving the diversification of Cry proteins may be in an attempt to adapt for the "arm race" between delta-endotoxins and the targeted insects, or to enlarge their target spectra, hence result in the functional divergence. The sites identified to be under positive selection would provide targets for further structural and functional analyses on Cry proteins.