Aim Sarcopenia is a robust prognostic indicator of outcomes after surgery for colorectal cancer (CRC). However, there are no serum markers routinely available for estimating skeletal muscle mass (SMM). The present study aimed to describe a new sarcopenia index (SI), serum creatinine (Scr) 9 cystatin C-based glomerular filtration rate, and investigate its association with shortterm complications after curative resection of CRC.Method Consecutive patients who underwent curative resection of CRC from December 2011 to January 2017 were retrospectively identified. Skeletal muscle cross-sectional area was analysed on L3 computed tomographic images. Receiver operating characteristic curve analysis showed that the cutoff points of SI for sarcopenia were below 56.1 in men and below 43.7 in women. Patients were classified into low and high SI groups in accordance with these cutoff values. The association between SI and body composition and the impact of preoperative SI on postoperative outcomes were analysed.Results Among 417 patients, SI showed a stronger correlation with skeletal muscle area (SMA) (r = 0.537, P < 0.001) than with the Scr/cystatin C ratio (r = 0.469, P < 0.001) and Scr (r = 0.447, P < 0.001). The low SI group had a lower SMA, lower preoperative haemoglobin, a higher prevalence of sarcopenia and experienced more postoperative complications compared with the high SI group (all P < 0.001). Multivariate logistic regression analysis showed that the independent risk factors for overall complications were low preoperative haemoglobin, low SI, sarcopenia and American Society of Anesthesiologists grade ≥ 3.Conclusion This new SI is a simple and useful surrogate marker for estimating SMM, and is associated with outcomes after CRC surgery.What does this paper add to the literature? We describe a novel, simple approach with which to diagnose sarcopenia. The new sarcopenia index (SI), serum creatinine 9 cystatin C-based glomerular filtration rate, is closely associated with skeletal muscle mass. A low SI is an independent risk factor for postoperative complications after curative resection of colorectal cancer.
Significance and Impact of the Study: Colistin has been reported to be effective in selective digestive decontamination (SDD), which is an infection prevention measure used in the treatment of certain patients in intensive care. We are the first to report that colistin-induced intestinal dysbacteriosis can injure intestinal mucosal barrier function and increase bacterial translocation, whereas a high dose of colistin does not damage the intestinal mucosal barrier in germ-free (GF) mice raised in a GF environment. These results may indicate that prolonged use of a high dose of a SDD medication should be carefully considered. AbstractThe purpose of this study was to determine the effect of colistin-induced intestinal dysbacteriosis on intestinal mucosal barrier function and bacterial translocation in a mouse model. Colistin or saline was administered orally for 7 days, and populations of viable organisms from the caecal mucosa and its content, the ileal segments, the mesenteric lymph nodes (MLNs) and the internal organs were prepared for examination. In the intestinal dysbacteriosis model, intestinal barrier dysfunction was observed and associated with increased bacterial translocation to extraintestinal sites. The extent of bacterial translocation to the MLNs and internal organs in the colistin group was significantly higher than in the saline group. Colistin-induced intestinal dysbacteriosis was shown to injure the intestinal mucosa barrier function and increase bacterial dislocation.
Here, we report the identification and characterization of a novel tyrosine phosphorylation site in the carboxy-terminal Src Homology 3 (SH3) (SH3C) domain of the Crk adaptor protein. Y251 is located in the highly conserved RT loop structure of the SH3C, a region of Crk involved in the allosteric regulation of the Abl kinase. Exploiting kinase assays to show that Y251 is phosphorylated by Abl in vitro, we generated affinity-purified antisera against phosphorylated Y251 in Crk and showed that Abl induces phosphorylation at Y251 in vivo, and that the kinetics of phosphorylation at Y251 and the negative regulatory Y221 site in vitro are similar. Y251 on endogenous Crk was robustly phosphorylated in chronic myelogenous leukemia cell lines and in A431 and MDA-MB-468 cells stimulated with epidermal growth factor. Using streptavidin–biotin pull downs and unbiased high-throughput Src Homology 2 (SH2) profiling approaches, we found that a pY251 phosphopeptide binds specifically to a subset of SH2 domains, including Abl and Arg SH2, and that binding of pY251 to Abl SH2 induces transactivation of Abl 1b. Finally, the Y251F Crk mutant significantly abrogates Abl transactivation in vitro and in vivo. These studies point to a yet unrealized positive regulatory role resulting from tyrosine phosphorylation of Crk, and identify a novel mechanism by which an adaptor protein activates a non-receptor tyrosine kinase by SH2 domain displacement.
The mechanism of asthenozoospermia remains unclear. The knowledge of the metabolism of fatty acids in seminal plasma is important and meaningful for the pathological study of asthenozoospermia. We present an optimised assay of extraction and derivatisation followed by GC/MS to analyse metabolites, especially fatty acids, in seminal plasma from healthy and asthenozoospermic men. Eighty-nine peaks including 17 kinds of fatty acids were analysed and identified in the chromatogram. The GC/MS data were analysed using t test, fold change and partial least squares discriminant analysis to explore the potential biomarkers of asthenozoospermia. Seven metabolites in asthenozoospermic group were found to be significantly different from those in the normal group (with p < .05, fold change >1.2 and variable importance for projection >1). Of which, high levels of oleic acid and palmitic acid in seminal plasma from asthenozoospermic men may indicate a membrane metabolism disorder in spermatozoa and the lack of valine in the asthenozoospermic group may contribute to poor sperm motility. The results may facilitate the understanding of the role of fatty acids and amino acids in asthenozoospermia and provide solid foundation for further pathological study of asthenozoospermia.
Epitaxial film quality is critical to the success of high-performance a-Ga 2 O 3 vertical power devices. In this work, the origins of threading dislocation generation and annihilation in thick a-Ga 2 O 3 films heteroepitaxially grown on sapphire by the mist-CVD technique have been examined by means of high-resolution X-ray diffraction and transmission electron microscopies. By increasing the nominal thickness, screw dislocations exhibit an independent characteristic with a low density of about 1.8 Â 10 6 cm À2 , while edge dislocations propagating along the c-axis are dominant, which decrease down to 2.1 Â 10 9 cm À2 in density for an 8 lm-thick a-Ga 2 O 3 layer and exhibit an inverse dependence on the thickness. In the framework of the glide analytical model, parallel edge dislocations are generated at the interface due to the misfitinduced strain relaxation, while the dislocation glide and coalescence result in the annihilation and fusion behaviors. The optimal thick a-Ga 2 O 3 with low dislocation densities may provide a prospective alternative to fully realize a-Ga 2 O 3 power devices.
Eimeria tenella microneme protein 1 (EtMIC-1) is highly conserved with TgMIC-2, which is involved in parasite binding specifically to host cells. Little is known about the immune responses and protective efficacy against E. tenella infection with EtMIC-1 antigen. In the present study, the recombinant proteins of E. tenella mature MIC-1 and adhesive domain (von Willebrand factor type A domain, EtMIC-1-VD) were obtained, protective efficacy against E.tenella infection and the mucosal immune response, which is induced in broilers was evaluated. The antibody levels and the transcription profiles of cytokine of chickens, such as interleukin-12 (IL-12) and interferon-γ (IFN-γ), were detected after being immunized three times with the recombinant EtMIC-1 and EtMIC-1-VD by ELISA assay and quantitative real-time PCR, respectively. The results showed that both groups of chickens, after being immunized with 100 μg EtMIC-1 or EtMIC-1-VD antigen, induced about tenfold higher IgG levels compared to the nonimmune groups. The transcription profiles of IL-12 and IFN-γ of the immunized groups were significantly higher than the control groups as well. The anticoccidial index of the group immunized with 100 μg EtMIC-1 and the group immunized with 100 μg EtMIC-1-VD were 167.2 and 165.5, respectively, which are significantly higher than low-dose immunized groups and challenged control groups. Our data suggests that VD domain is the key functional structure of EtMIC-1 that could trigger a significant humoral and cellular response against E. tenella infection, and EtMIC-1 had the potential in imparting partial protection in chickens against homologous challenge.
Polarized Fourier transform infrared (FTIR) spectroscopy is employed to study the segmental orientation and mobility of liquid-crystalline elastomers (LCEs) with a monodomain structure in response to external mechanical fields parallel and perpendicular to the initial nematic director. The mean orientation and the molecular order parameter of the different molecular moieties referring to the mesogen, the spacer and the network are analyzed in detail. Parallel stretch leaves the mean orientation of the different molecular moieties and its molecular order parameter nearly uninfluenced. Perpendicular stretch results in a threshold-like dependence: for elongation ratios lambda < or = lambda(c) = 1.3 (10 mol% crosslinker density), respectively lambda < or = lambda(c) = 1.6 (5 mol% crosslinker density) no change of the mean orientation and the molecular order parameters is observed, while for lambda > or = lambda(c) all molecular units reorient and their molecular order parameters are strongly decreased. The present studies give no indications that the reorientational dynamics of the network and the mesogens differ as long as the elongation ratio is smaller than lambda(c).
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