catena-Poly[[[bis­[4-(1H-1,3,7,8-tetra­azacyclo­penta­[l]phenanthren-2-yl)phenol-κ2 N 7,N 8]manganese(II)]-μ-naphthalene-1,4-dicarboxyl­ato-κ2 O 1:O 4] naphthalene-1,4-dicarboxylic acid hemisolvate monohydrate]

The 1,4-dicarboxyl­ate dianions in the title compound, [Mn(C12H6O4)(C19H12N4O)2]·0.5C12H8O4·H2O, bond to two 4-(1H-1,3,7,8-tetra­azacyclo­penta­[l]phenanthren-2-yl)phenol-chelated Mn atoms to form a chain that features the metal atom in an octa­hedral coordination geometry. Adjacent chains inter­act with the uncoordinated water mol­ecules to form a three-dimensional network. The naphthalene-1,4-dicarboxylic acid solvent mol­ecule, which is disordered about a centre of inversion, occupies the space within the network but is not bonded to the network. One NH group is disordered equally over two positions

Occurrence and Biodegradation of Nonylphenol in the Environment

Nonylphenol (NP) is an ultimate degradation product of nonylphenol polyethoxylates (NPE) that is primarily used in cleaning and industrial processes. Its widespread use has led to the wide existence of NP in various environmental matrices, such as water, sediment, air and soil. NP can be decreased by biodegradation through the action of microorganisms under aerobic or anaerobic conditions. Half-lives of biodegradation ranged from a few days to almost one hundred days. The degradation rate for NP was influenced by temperature, pH and additions of yeast extracts, surfactants, aluminum sulfate, acetate, pyruvate, lactate, manganese dioxide, ferric chloride, sodium chloride, hydrogen peroxide, heavy metals, and phthalic acid esters. Although NP is present at low concentrations in the environment, as an endocrine disruptor the risks of long-term exposure to low concentrations remain largely unknown. This paper reviews the occurrence of NP in the environment and its aerobic and anaerobic biodegradation in natural environments and sewage treatment plants, which is essential for assessing the potential risk associated with low level exposure to NP and other endocrine disruptors

Dichlorido(dipyrido[3,2-a:2′,3′-c]phenazine)manganese(II)

The complete mol­ecule of the title compound, [MnCl2(C18H10N4)2], is generated by crystallographic twofold symmetry with the Mn atom lying on the rotation axis. The Mn coordination geometry is a distorted cis-MnCl2N4 octa­hedron, arising from two N,N′-bidentate dipyrido[3,2-a:2′,3′-c]phenazine (DPPZ) ligands and two chloride ions. In the crystal structure, neighbouring mononuclear units pack together through π–π contacts between the DPPZ rings [shortest centroid–centroid distance = 3.480 (2) Å], leading to a chain-like structure along [001]. C—H⋯Cl hydrogen bonds complete the structure

Bis[3,5-difluoro-2-(2-pyrid­yl)phen­yl](picolinato)iridium(III)

The Ir centre in the title complex, [Ir(C11H6F2N)2(C6H4NO2)], is six-coordinated in a slightly distorted octa­hedral IrC2N3O fashion

Immunoglobulin G4-related disease complicated with vascular lesions: CT findings in 21 patients

PURPOSE:We aimed to analyze multislice computed tomography (MSCT) imaging features of vasculitis in immunoglobulin G4-related disease (IgG4-RD).METHODS:In this retrospective study, we diagnosed 21 definite or possible IgG4-RD patients (71.4% male; mean age, 52.1±4.5 years) with vasculitis by MSCT and pathologic examination. The clinical background, laboratory analysis, pathologic results, CT images, and response to therapy were assessed and analyzed.RESULTS:Under enhanced MSCT, 50 vasculitic lesions were identified and were divided into five types (types A–E) according to the CT findings on the basis of luminal changes. There were more vasculitic lesions observed below the diaphragm (n=30) than above it (n=20). Aneurysms and aneurysmal dilatation were more likely to be found in the aortaventralis (n=5), aortic arch (n=3) and iliac arteries (n=3). Most of the vascular lesions were characterized by wall thickening with a normal lumen (n=15) and slight stenosis (n=22). The affected vascular walls were all thickened between 4 and 18 mm. The walls of 19 patients (90.4%) were well circumscribed. The wall thickness of the aorta, including the aortaventralis and aortic arch, was more notable than that of the other vascular sites. Fourteen patients were followed up for 2–24 months. Wall thickness decreased in all cases. The average maximum thicknesses before and after therapy were 12.2±2.7 mm and 6.1±1.8 mm, which were significantly different (P < 0.001). The lumens of two patients were found to be slightly enlarged, while those of the other cases were unchanged after therapy.CONCLUSION:IgG4-RD vascular lesions can be divided into five types, which are more likely to be present in the aorta and its main branches, and can rapidly diminish after steroid therapy. The lumen may be unchanged or slightly enlarged

Single cell epigenomic and transcriptomic analysis uncovers potential transcription factors regulating mitotic/meiotic switch

In order to reveal the complex mechanism governing the mitotic/meiotic switch in female germ cells at epigenomic and genomic levels, we examined the chromatin accessibility (scATAC-seq) and the transcriptional dynamics (scRNA-seq) in germ cells of mouse embryonic ovary between E11.5 to 13.5 at single-cell resolution. Adopting a strict transcription factors (TFs) screening framework that makes it easier to understand the single-cell chromatin signature and a TF interaction algorithm that integrates the transcript levels, chromatin accessibility, and motif scores, we identified 14 TFs potentially regulating the mitotic/meiotic switch, including TCFL5, E2F1, E2F2, E2F6, E2F8, BATF3, SP1, FOS, FOXN3, VEZF1, GBX2, CEBPG, JUND, and TFDP1. Focusing on TCFL5, we constructed Tcfl5(+/-) mice which showed significantly reduced fertility and found that decreasing TCFL5 expression in cultured E12.5 ovaries by RNAi impaired meiotic progression from leptotene to zygotene. Bioinformatics analysis of published results of the embryonic germ cell transcriptome and the finding that in these cells central meiotic genes (Stra8, Tcfl5, Sycp3, and E2f2) possess open chromatin status already at the mitotic stage together with other features of TCFL5 (potential capability to interact with core TFs and activate meiotic genes, its progressive activation after preleptotene, binding sites in the promoter region of E2f2 and Sycp3), indicated extensive amplification of transcriptional programs associated to mitotic/meiotic switch with an important contribution of TCFL5. We conclude that the identified TFs, are involved in various stages of the mitotic/meiotic switch in female germ cells, TCFL5 primarily in meiotic progression. Further investigation on these factors might give a significant contribution to unravel the molecular mechanisms of this fundamental process of oogenesis and provide clues about pathologies in women such as primary ovarian insufficiency (POI) due at least in part to meiotic defects

Exosomes: potential diagnostic markers and drug carriers for adenomyosis

Adenomyosis is a common benign gynecological disorder and an important factor leading to infertility in fertile women. Adenomyosis can cause deep lesions and is persistent and refractory in nature due to its tumor-like biological characteristics, such as the ability to implant, adhere, and invade. The pathogenesis of adenomyosis is currently unclear. Therefore, new therapeutic approaches are urgently required. Exosomes are nanoscale vesicles secreted by cells that carry proteins, genetic materials and other biologically active components. Exosomes play an important role in maintaining tissue homeostasis and regulating immune responses and metabolism. A growing body of work has shown that exosomes and their contents are key to the development and progression of adenomyosis. This review discusses the current research progress, future prospects and challenges in this emerging therapeutic tool by providing an overview of the changes in the adenomyosis uterine microenvironment and the biogenesis and functions of exosomes, with particular emphasis on the role of exosomes and their contents in the regulation of cell migration, proliferation, fibrosis formation, neovascularization, and inflammatory responses in adenomyosis

Isolation, identification, and complete genome sequence of a bovine adenovirus type 3 from cattle in China

<p>Abstract</p> <p>Background</p> <p>Bovine adenovirus type 3 (BAV-3) belongs to the <it>Mastadenovirus </it>genus of the family <it>Adenoviridae </it>and is involved in respiratory and enteric infections of calves. The isolation of BAV-3 has not been reported prior to this study in China. In 2009, there were many cases in cattle showing similar clinical signs to BAV-3 infection and a virus strain, showing cytopathic effect in Madin-Darby bovine kidney cells, was isolated from a bovine nasal swab collected from feedlot cattle in Heilongjiang Province, China. The isolate was confirmed as a bovine adenovirus type 3 by PCR and immunofluorescence assay, and named as HLJ0955. So far only the complete genome sequence of prototype of BAV-3 WBR-1 strain has been reported. In order to further characterize the Chinese isolate HLJ0955, the complete genome sequence of HLJ0955 was determined.</p> <p>Results</p> <p>The size of the genome of the Chinese isolate HLJ0955 is 34,132 nucleotides in length with a G+C content of 53.6%. The coding sequences for gene regions of HLJ0955 isolate were similar to the prototype of BAV-3 WBR-1 strain, with 80.0-98.6% nucleotide and 87.5-98.8% amino acid identities. The genome of HLJ0955 strain contains 16 regions and four deletions in inverted terminal repeats, E1B region and E4 region, respectively. The complete genome and DNA binding protein gene based phylogenetic analysis with other adenoviruses were performed and the results showed that HLJ0955 isolate belonged to BAV-3 and clustered within the <it>Mastadenovirus </it>genus of the family <it>Adenoviridae</it>.</p> <p>Conclusions</p> <p>This is the first study to report the isolation and molecular characterization of BAV-3 from cattle in China. The phylogenetic analysis performed in this study supported the use of the DNA binding protein gene of adenovirus as an appropriate subgenomic target for the classification of different genuses of the family <it>Adenoviridae </it>on the molecular basis. Meanwhile, a large-scale pathogen and serological epidemiological investigations for BVA-3 infection might be carried out in cattle in China. This report will be a good beginning for further studies on BAV-3 in China.</p

Radiosensitization and growth inhibition of cancer cells mediated by an scFv antibody gene against DNA-PKcs in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>Overexpression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is commonly occurred in cancers and causes radioresistance and poor prognosis. In present study, the single-chain variable antibody fragments (scFv) targeting DNA-PKcs was developed for the application of radiosensitization in vitro and in vivo. A humanized semisynthetic scFv library and the phage-display antibodies technology were employed to screen DNA-PKcs scFv antibody.</p> <p>Methods</p> <p>DNA-PKcs epitopes were predicted and cloned. A humanized semisynthetic scFv library and the phage-display antibodies technology were employed to screen DNA-PKcs scFv antibody. DNA damage repair was analyzed by comet assay and immunofluorescence detection of γH2AX foci. The radiosensitization in vivo was determined on Balb/c athymic mice transplanted tumours of HeLa cells.</p> <p>Results</p> <p>Four epitopes of DNA-PKcs have been predicted and expressed as the antigens, and a specific human anti-DNA-PKcs scFv antibody gene, anti-DPK3-scFv, was obtained by screening the phage antibody library using the DNA-PKcs peptide DPK3. The specificity of anti-DPK3-scFv was verified, <it>in vitro</it>. Transfection of HeLa cells with the anti-DPK3-scFv gene resulted in an increased sensitivity to IR, decreased repair capability of DNA double-strand breaks (DSB) detected by comet assay and immunofluorescence detection of γH2AX foci. Moreover, the kinase activity of DNA-PKcs was inhibited by anti-DPK3-scFv, which was displayed by the decreased phosphorylation levels of its target Akt/S473 and the autophosphorylation of DNA-PKcs on S2056 induced by radiation. Measurement of the growth and apoptosis rates showed that anti-DPK3-scFv enhanced the sensitivity of tumours transplanted in Balb/c athymic mice to radiation therapy.</p> <p>Conclusion</p> <p>The antiproliferation and radiosensitizing effects of anti-DPK3-scFv via targeting DNA-PKcs make it very appealing for the development as a novel biological radiosensitizer for cancer therapeutic potential.</p

A Stem Cell-Based Tool for Small Molecule Screening in Adipogenesis

Techniques for small molecule screening are widely used in biological mechanism study and drug discovery. Here, we reported a novel adipocyte differentiation assay for small molecule selection, based on human mesenchymal stem cells (hMSCs) transduced with fluorescence reporter gene driven by adipogenic specific promoter - adipocyte Protein 2 (aP2; also namely Fatty Acid Binding Protein 4, FABP4). During normal adipogenic induction as well as adipogenic inhibition by Ly294002, we confirmed that the intensity of green fluorescence protein corresponded well to the expression level of aP2 gene. Furthermore, this variation of green fluorescence protein intensity can be read simply through fluorescence spectrophotometer. By testing another two small molecules in adipogenesis –Troglitazone and CHIR99021, we proved that this is a simple and sensitive method, which could be applied in adipocyte biology, drug discovery and toxicological study in the future