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A total synthesis approach of CS-E oligosaccharides was established and a series of derivatives were synthesized. These oligosaccharides were evaluated for a glycosaminoglycan (GAG)-binding protein interaction against cytokines, midkine, and pleiotrophin, by surface-plasmon resonance (SPR) assay. The binding epitopes of oligosaccharides to midkine were mapped using a saturation transfer difference (STD) NMR technique. The groups on the reducing end contributed to binding affinity, and should not be ignored in biological assays. These findings contribute to the structure and activity relationship research and a foundation of understanding that will underpin potential future optimization of this class of oligosaccharides as pharmaceutical agents. [ABSTRACT FROM AUTHOR]

On the basis of the C60 high-strength fair-faced concrete mix ratio, the effects of the total amount of cementitious materials, slag powder content, silica fume content, water binder ratio and different particle size coarse aggregate content on the workability, mechanical properties and clean water effect of high-strength fair-faced concrete are studied by orthogonal test and image processing technology. The results are as follows, the influence degree on the slump of fair-faced concrete is as follows:total amount of cementitious materials>content of coarse aggregate with different particle sizes>content of slag powder>content of silica fume>water binder ratio, the degree of influence on the 28d compressive strength of fair-faced concrete is as follows:slag powder content>water binder ratio>total amount of cementitious materials>silica fume content>coarse aggregate content of different particle sizes, the influence degree on the effect of clean water is in the order of total amount of cementitious materials>silica fume content>slag powder content>water binder ratio>coarse aggregate content of different particle sizes. [ABSTRACT FROM AUTHOR]

To investigate the influence of heating temperature on the evolution of physical and chemical structures of thermal interpreted emissions and solid phase residues in tobacco under low-oxygen atmosphere, a tubular furnace reactor was used to capture the smoke components of reconstituted tobacco leaves at different heating temperatures under low oxygen concentration and prepare solid phase residues. Representative smoke components were detected by GC-MS, and various analysis and characterization techniques were used to detect the microstructure and chemical composition of solid phase residues. The results showed that during the heating process of reconstituted tobacco leaves, the basic substances such as glycerol, propylene glycol, and nicotine were mostly directly transferred to the smoke aerosol after being heated. The release of crotonaldehyde, hydroxyacetone, isoprene, and benzene derivatives increased with increasing temperature, while the release of naphthalene decreased with increasing temperature. Phenolic ketone components such as guaiacol, cresol, phenol, 2,3-butanedione, 1-hydroxy-2-butanone, and 2 (5H)-furanone exhibited fluctuations with temperature changes; The representative volatile compounds represented by low-temperature cracking of isoprene in flue gas increase with the increase of temperature; The degree of ashing of the solid residue fiber skeleton increases with the increase of temperature; Before 370 °C, the reconstituted tobacco leaves were mainly characterized by volatilization, distillation, and the dehydroxylation/decarboxylation of hemicellulose and cellulose. With the increase of temperature, there was an oxidation reaction in the pyrolysis process, and the proportion of more stable oxygen containing functional groups on the surface of the reconstituted tobacco leaves increased sharply. [ABSTRACT FROM AUTHOR]

Objective: Inflammation plays a key role in the etiology and pathology of postoperative cognitive dysfunction (POCD). Cyclooxygenase (COX)-2 inhibitor celecoxib is used for the treatment of acute pain due to its potent anti-inflammatory and analgesic effects. Herein, we evaluated the effects of celecoxib on POCD in geriatric patients.Methods: A total of 178 geriatric patients undergoing total knee arthroplasty were randomly divided into two groups and treated with celecoxib (group C) or placebo (group P). The levels of perioperative plasma COX-2, IL-1β, IL-6, TNF-α, neuron-specific enolase, and S100β were detected in all patients. The pain intensity was measured by numerical rating scale (NRS). A battery of 9 neuropsychological tests was performed pre-operatively and 1 week, and 3 months postoperatively. Patients, whose postoperative performance declined by ≧1 standard deviation as compared to each preoperative test score on ≧2 tests, were classified as POCD.Results: A significant decrease in POCD incidence was found in group C as compared to group P on postoperative day 7 (12.3% vs. 34.1%; p < 0.05). POCD incidence did not differ between the two groups at the 3-month follow-up (8.8 vs. 9.7%). NRS scores at days 3 and 4 post-surgery were significantly lower in group C (p < 0.05). Patients in group C showed lower level of plasma COX-2, IL-1β, IL-6, TNF-α, and S100β as compared to group P postoperatively (p < 0.05).Conclusion: These results demonstrated that celecoxib can decrease early POCD incidence after total knee arthroplasty in geriatric patients, which might be mediated by suppressing inflammation and acute postoperative pain caused by surgical trauma.Registration: Chinese Clinical Trial Register, ChiCTR-IOR-16008168.

[This corrects the article DOI: 10.1371/journal.pone.0182866.].

A large number of SARS-related coronaviruses (SARSr-CoV) have been detected in horseshoe bats since 2005 in different areas of China. However, these bat SARSr-CoVs show sequence differences from SARS coronavirus (SARS-CoV) in different genes (S, ORF8, ORF3, etc) and are considered unlikely to represent the direct progenitor of SARS-CoV. Herein, we report the findings of our 5-year surveillance of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China. The full-length genomes of 11 newly discovered SARSr-CoV strains, together with our previous findings, reveals that the SARSr-CoVs circulating in this single location are highly diverse in the S gene, ORF3 and ORF8. Importantly, strains with high genetic similarity to SARS-CoV in the hypervariable N-terminal domain (NTD) and receptor-binding domain (RBD) of the S1 gene, the ORF3 and ORF8 region, respectively, were all discovered in this cave. In addition, we report the first discovery of bat SARSr-CoVs highly similar to human SARS-CoV in ORF3b and in the split ORF8a and 8b. Moreover, SARSr-CoV strains from this cave were more closely related to SARS-CoV in the non-structural protein genes ORF1a and 1b compared with those detected elsewhere. Recombination analysis shows evidence of frequent recombination events within the S gene and around the ORF8 between these SARSr-CoVs. We hypothesize that the direct progenitor of SARS-CoV may have originated after sequential recombination events between the precursors of these SARSr-CoVs. Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, further exhibiting the close relationship between strains in this cave and SARS-CoV. This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases.

Bats are important reservoirs of many viruses, which are capable of infecting the host without inducing obvious clinical diseases. Interferon and the downstream interferon regulated genes (IRGs) are known to act as the first line of defense against viral infections. Little is known about the transcriptional profile of genes being induced by interferon in bats and their role in controlling virus infection. In this study, we constructed IFNAR2 knockout bat cell lines using CRISPR technology and further characterized gene expression profiles induced by the most abundant IFN-α (IFN-α3). Firstly, we demonstrated that the CRISPR/Cas9 system is applicable for bat cells as this represents the first CRIPSR knockout cell line for bats. Our results showed the pleiotropic effect of IFN-α3 on the bat kidney cell line, PaKiT03. As expected, we confirmed that IFNAR2 is indispensable for IFN-a signaling pathway and plays an important role in antiviral immunity. Unexpectedly, we also identified novel IFNAR2-dependent IRGs which are enriched in pathways related to cancer. To our knowledge, this seems to be bat-specific as no such observation has been reported for other mammalian species. This study expands our knowledge about bat immunology and the cell line established can provide a powerful tool for future study into virus-bat interaction and cancer biology.