circular RNA circ-231 promotes protein biogenesis of TPI1 and PRDX6 through mediating the interaction of eIF4A3 with STAU1 to facilitate unwinding of secondary structure in 5' UTR, enhancing progression of human esophageal squamous cell carcinoma (ESCC).

Background: The nuclear cap-binding complex (CBC)-dependent translation (CT) is an important initial translation pathway for 5'-cap-dependent translation in normal mammal cells. Eukaryotic translation initiation factor 4A-III (eIF4A3), as an RNA helicase, is recruited to CT complex and enhances CT efficiency through participating in unwinding of secondary structure in the 5' UTR. However, the detailed mechanism for eIF4A3 implicated in unwinding of secondary structure in the 5' UTR in normal mammal cells is still unclear. Specially, we need to investigate whether the kind of mechanism in normal mammal cells extrapolates to cancer cells, e.g. ESCC, and further interrogate whether and how the mechanism triggers malignant phenotype of ESCC, which are important for identifying a potential therapeutic target for patients with ESCC. Methods: Bioinformatics analysis, RNA immunoprecipitation and RNA pulldown assays were performed to detect the interaction of circular RNA circ-231 with eIF4A3. In vitro and in vivo assays were performed to detect biological roles of circ-231 in ESCC. RNA immunoprecipitation, RNA pulldown, mass spectrometry analysis and co-immunoprecipitation assays were used to measure the interaction of circ-231, eIF4A3 and STAU1 in HEK293T and ESCC. In vitro EGFP reporter and 5' UTR of mRNA pulldown assays were performed to probe for the binding of circ-231, eIF4A3 and STAU1 to secondary structure of 5' UTR. Results: RNA immunoprecipitation assays showed that circ-231 interacted with eIF4A3 in HEK293T and ESCC. Further study confirmed that circ-231 orchestrated with eIF4A3 to control protein expression of TPI1 and PRDX6, but not for mRNA transcripts. The in-depth mechanism study uncovered that both circ-231 and eIF4A3 were involved in unwinding of secondary structure in 5' UTR of TPI1 and PRDX6. More importantly, circ-231 promoted the interaction between eIF4A3 and STAU1. Intriguingly, both circ-231 and eIF4A3 were dependent on STAU1 binding to secondary structure in 5' UTR. Biological function assays revealed that circ-231 promoted the migration and proliferation of ESCC via TPI1 and PRDX6. In ESCC, the up-regulated expression of circ-231 was observed and patients with ESCC characterized by higher expression of circ-231 have concurrent lymph node metastasis, compared with control. Conclusions: Our data unravels the detailed mechanism by which STAU1 binds to secondary structure in 5' UTR of mRNAs and recruits eIF4A3 through interacting with circ-231 and thereby eIF4A3 is implicated in unwinding of secondary structure, which is common to HEK293T and ESCC. However, importantly, our data reveals that circ-231 promotes migration and proliferation of ESCC and the up-regulated circ-231 greatly correlates with tumor lymph node metastasis, insinuating that circ-231 could be a therapeutic target and an indicator of risk of lymph node metastasis for patients with ESCC.

Facile Fabrication of Hollow Nanoporous Carbon Architectures by Controlling MOF Crystalline Inhomogeneity for Ultra-Stable Na-Ion Storage.

Hollow nanoporous carbon architectures (HNCs) present significant utilitarian value for a wide variety of applications. Facile and efficient preparation of HNCs has long been pursued but still remains challenging. Herein, we for the first time demonstrate that single-component metal-organic frameworks (MOFs) crystals, rather than the widely reported hybrid ones which necessitate tedious operations for preparation, could enable the facile and versatile syntheses of functional HNCs. By controlling the growth kinetics, the MOFs crystals (STU-1) are readily engineered into different shapes with designated styles of crystalline inhomogeneity. A subsequent one-step pyrolysis of these MOFs with intraparticle difference can induce a simultaneous self-hollowing and carbonization process, thereby producing various functional HNCs including yolk-shell polyhedrons, hollow microspheres, mesoporous architectures, and superstructures. Superior to the existing methods, this synthetic strategy relies only on the complex nature of single-component MOFs crystals without involving tedious operations like coating, etching, or ligand exchange, making it convenient, efficient, and easy to scale up. An ultra-stable Na-ion battery anode is demonstrated by the HNCs with extraordinary cyclability (93 % capacity retention over 8000 cycles), highlighting a high level of functionality of the HNCs.

Multiple Accessible Redox-Active Sites in a Robust Covalent Organic Framework for High-Performance Potassium Storage.

Covalent organic framework (COF) materials with porous character and robust structure have significant applied implications for K-ion battery (KIB) anodes, but they are limited by the low reversible capacity and inferior rate capability. Here, based on theoretical calculations, we identified that a porous bulk COF featuring numerous pyrazines and carbonyls in the π-conjugated periodic skeleton could provide multiple accessible redox-active sites for high-performance potassium storage. Its porous structure with a surface-dominated storage mechanism enabled the fast and stable storage of K-ions. Its insolubility in organic electrolytes and small volumetric change after potassiation ensured a robust electrode for stable cycling. As a KIB anode, this bulk COF demonstrated an unprecedentedly outstanding combination of reversible capacity (423 mAh g-1 at 0.1 C), rate capability (185 mAh g-1 at 10 C), and cyclability. The theoretical simulation and comprehensive characterizations confirmed the active sites are contributed by C═O, C═N, and the cation-π effect.

Engineering Microstructure of a Robust Polymer Anode by Moderate Pyrolysis for High-Performance Sodium Storage.

Polymer anodes have inspired considerable research interest for Na-ion batteries (NIBs) owing to their high structural flexibility and resource sustainability but are limited by the sluggish electrode kinetics, insufficient cyclability, and inferior electronic conductivity which usually made a large fraction (20-50 wt %) of conductive carbon additive necessitated. Herein, using a polymeric carbon nitride (PCN) anode as an example, we demonstrated that a moderate pyrolysis of the polymer anode could not only reduce its optical bandgap to enhance its electronic conductivity but also tune its microstructures to facilitate Na+ transfer/storage and sustain the repeated sodiation/desodiation. When used as NIBs anode with 10 wt % conductive carbon adding for preparing the electrode film, the moderate-pyrolysis PCN can promise high specific capacity (351 mAh g-1 at 0.1C), superb rate capability (151 and 95 mAh g-1 at 10C and 20C, respectively), and ultrastable cyclability (88.5% capacity retention after 6500 cycles at 2C). This comprehensive battery performance is much better than that of the previously reported organic counterparts. Our finding opened a new avenue in designing high-performance polymer anode for Na-ion batteries.

[Effect of Intercellular Adhesion Molecule-1 on Adherence Between Mesenchymal Stem Cells and Endothelial Progenitor Cells].

OBJECTIVE: To investigate the effects of intercellular adhesion molecule-1(ICAM-1) on the adherence between mesenchymal stem cells (MSC) and endothelial progenitor cells (EPC). METHODS: MSC and EPC were isolated, cultured and expanded from the 6-8 weeks aged C57BL/6 murine bone marrow by in vitro. Immuno-fluorescence was used to detect the expression of ICAM-1 in MSC group, EPC group and co-cultured MSC and EPC group. The mRNA and protein levels of ICAM-1 were detected by RT-PCR and Western blot respectively, then, the ICAM-1 adherence between MSC and EPC was observed by adding different concentration of neutralizing antibody. RESULTS: The expression of ICAM-1 on surface of MSC and EPC could be detected by cell immunofluorescence method. According to results of the semiquantitative fluorescene detection, the fluorescence strength of MSC+EPC co-cultured group (89.02 ± 24.52) was higher than that of MSC group (31.25 ± 2.95) and EPC group (34.32 ± 5.02), and there was statistical difference between them (P < 0.01), but there was no obvious difference between MSC group and EPC group (P > 0.05). RT-PCR detection showed that the expression levels of ICAM-1 in MSC+EPC co-cultured group were higher than that in MSC group and that in EPC group (P < 0.01), and expression level of ICAM in EPC group was higher than that in MSC group (P < 0.01). Western blot detection showed that the expression level of ICAM-1 protein in MSC+EPC co-cultured group (0.33 ± 0.4) was higher than that in MSC group (0.11 ± 0.01) (P < 0.05) and than that in EPC group (0.19+0.02) (P < 0.05), However, the expression level of ICAM-1 protein in EPC group was higher than that in MSC group (P < 0.05). The test of different concentrations against neutralizing antibody showed that with the increasing of concentration of ICAM-1 neutralizing antibody, the adhesion capability of MSC and EPC was gradually decreasing. CONCLUSION: The ICAM-1 can mediate the adherence process between MSC and EPC.

Changes in relative organ weights and intestinal transporter gene expression in embryos from White Plymouth Rock and WENS Yellow Feather Chickens.

This study was conducted to evaluate the embryonic development of broilers with different growth rates and correlate the differences between the amino acid transporter and peptide transporter gene expression patterns to the growth of the small intestine. The results showed that the body and yolk weights of the White Plymouth Rock (WPR) embryos were higher than those of the WENS Yellow Feather Chicken (WYFC) embryos although the relative embryonic body weights were inversely correlated. We studied nine organs and classified them into four clusters according to their changes in relative weight during the hatching process. The levels of gene expression of SLC7A9, SLC1A1 and SLC15A1 in the small intestine increased during embryo development and were affected by breed. Breed-specific differences in embryonic development were observed for SLC7A9, SLC1A1 and SLC15A1 gene expression. When represented as a function of SLC7A9, SLC1A1 or SLC15A1 gene expression, strong correlations were observed for the weight of small intestine. We conclude that WPR embryos have a higher absolute growth rate but a lower relative growth rate in comparison with WYFC embryos. Moreover, the expression levels of the SLC7A9, SLC1A1 or SLC15A1 genes can be used as indicators for the growth of the small intestine.

Net financial benefits of averting HIV infections among people who inject drugs in Urumqi, Xinjiang, Peoples Republic of China (2005-2010).

BACKGROUND: To quantify the contribution of locally implemented prevention programmes in contributing to reductions in treatment and care costs by averting HIV infections among those who inject drugs this study calculates net financial benefit of providing harm reduction programmes using information from services being implemented in Urumqi, Xinjiang Uighur Autonomous Region of China ( between 2005 and 2010). METHODS: Information was collected to assess cost of providing methadone treatment (MMT) and needle and syringe programmes (NSP). HIV incidence was estimated among people who inject drugs (PWID). HIV infections averted were calculated. Net benefit was assessed by estimating costs of providing prevention programmes and comparing these to the costs of providing care. RESULTS: An estimated 5678 (range 3982-7599) HIV infections were averted between 2005 and 2010 and the net financial benefit of providing harm reduction programmes compared to treatment and care costs for HIV infections averted was USD 4.383 million during the same time period. CONCLUSION: These results demonstrate the net and accumulating benefit of investing in harm reduction programmes for PWID in Urumqi. The return on investment progressively increased during the time period studied and it is clear that these cost savings will continue to accrue with the continued implementation of HIV prevention interventions in the community that include harm reduction programmes targeted at PWID.

[Effects of electrical stimulation of sciatic nerve on synaptic plasticity of spinal dorsal horn, hippocampal CA1 region and spinal c-fos, hippocampal CA1 region expression in neonatal rats].

OBJECTIVE: To explore the response to nociceptive stimuli in spinal cord of neonatal rat and observe the electrical stimulation of sciatic nerve on synaptic plasticity of spinal dorsal horn, hippocampal CA1 region and spinal c-fos, hippocampal CA1 region expression in neonatal rats. METHODS: The rats were divided into neonatal and adult groups. The evoked potentials of left spinal dorsal horn from T13-L1 and right hippocampal CA1 region were recorded. After conditional electric stimulations, the potential amplitudes were recorded. When the incubation period reached 120 min, D-AP5 was added to spinal cord of rats and resulting changes in field potential and c-fos expression were recorded. RESULTS: Long-term potentiation (LTP) in neonatal rats was mainly evoked by A-type nerve fibers whereas LTP in adult rats was mainly evoked by C-type nerve fibers. C-fos expression was significantly increased in superficial, deep layers of spinal dorsal horn, ventral horn and hippocampal CA1 region in neonatal rats. CONCLUSION: Pain signals change with age.

Pericyst may be a new pharmacological and therapeutic target for hydatid disease.

BACKGROUND: Most hydatid cysts with calcified walls are biologically and clinically silent and inactive. Transforming growth factor-beta 1 (TGF-ß1) plays a critical role in the calcification process of cells. The aim of this study was to assess the effect of modulating TGF-ß1 signaling on the calcification of hydatid cysts. METHODS: Pericyst cells isolated from hepatic hydatid cysts were cultured with osteogenic media. These cells were assessed for alkaline phosphatase activity and mineralization capacity using Alizarin Red staining. Cells were also treated with recombinant human TGF-ß1 and TGF-ß inhibitor, and the expression profiles of osteoblast markers (RUNX2, osterix, and osteocalcin) were analyzed using Western blotting. The effects of inhibiting TGF-ß1 signaling on calcification of pericyst walls were assessed using different doses of TGF-ß inhibitor for 7 weeks in a preclinical disease model of liver cystic echinococcosis. RESULTS: Cells within the pericyst displayed high levels of alkaline phosphatase activity and mineralized nodule formation, as induced by osteogenic media. These activities, as well as expression profiles of osteoblast markers (RUNX2, osterix, and osteocalcin) could be inhibited by addition of recombinant human TGF-ß1 (rhTGF-ß1) and enhanced by TGF-ß inhibitor. In the animal model of cystic echinococcosis, inhibition of TGF-ß1 signaling increased calcification of the pericyst wall, which was associated with decreased cyst load index and lower viability of protoscoleces. CONCLUSIONS: Cells within the pericysts adopt an osteoblast-like phenotype and have osteogenic potential. Inhibition of TGF-ß1 signaling increases hydatid cyst calcification. Pharmacological modulation of calcification in pericysts may be a new therapeutic target in the treatment of hydatid disease.