Low-dose rectal diclofenac can prevent PEP.

Sarcopenia is a risk factor for recurrence in patients with HCC who were treated with curative treatment.

The pentose phosphate pathway (PPP) plays an important role in the efficiency of xylose fermentation during cellulosic ethanol production. In simultaneous saccharification and co-fermentation (SSCF), the optimal temperature for cellulase hydrolysis of lignocellulose is much higher than that of fermentation. Successful use of SSCF requires optimization of the expression of PPP genes at elevated temperatures. This study examined the combinatorial expression of PPP genes at high temperature. The results revealed that over-expression of TAL1 and TKL1 in Saccharomyces cerevisiae (S. cerevisiae) at 30 °C and over-expression of all PPP genes at 36 °C resulted in the highest ethanol productivities. Furthermore, combinatorial over-expression of PPP genes derived from S. cerevisiae and a thermostable yeast Kluyveromyces marxianus allowed the strain to ferment xylose with ethanol productivity of 0.51 g/L/h, even at 38 °C. These results clearly demonstrate that xylose metabolism can be improved by the utilization of appropriate combinations of thermostable PPP genes in high-temperature production of ethanol.

BackgroundThe present study was performed to compare the safety of sedation during endoscopic submucosal dissection (ESD) in the endoscopy room versus operation room.MethodsIn total, 297 patients with gastrointestinal tumors who underwent ESD from January 2011 to December 2016 were retrospectively reviewed. The patients were divided into two groups: those who underwent ESD in the endoscopy room without propofol (Group E) versus operation room with propofol (Group O). The patient, tumor, and procedure characteristics; adverse events; and treatment outcomes were compared between the two groups.ResultsThe patient and tumor characteristics, including age (73.6 ± 8.2 vs. 72.5 ± 9.1 years), comorbidities, and tumor size and histology, were not different between Groups E and O. The ESD procedure time was comparable between Groups E and O (105.4 ± 70.4 vs. 106.5 ± 64.4 min), and the anesthesia time was equivalent (138.3 ± 78.1 vs. 148.4 ± 68.8 min). There were no significant differences in adverse events between the two groups. During the ESD procedure, desaturation occurred significantly more often in Group E than O (12.9% vs. 4.0%, P = 0.021, odds ratio: 3.53, 95% CI: 1.17–14.4). The recovery time after ESD was significantly longer in Group E than O (180 (100–360) vs. 90 (0–180) min, P < 0.001).ConclusionsA decreased desaturation rate and shorter recovery time after ESD were the advantages of sedation in the operation room with propofol compared with sedation in the endoscopy room. These findings warrant further exploration of the advantages of safe and effective ESD for upper gastrointestinal neoplasms in the operation room.

Isoniazid (INH) is one of the most effective antibiotics against tuberculosis. INH is a prodrug that is activated by KatG. Although extensive studies have been performed in order to understand the mechanism of KatG, even the binding site of INH in KatG remains controversial. In this study, we determined the crystal structure of KatG from Synechococcus elongatus PCC7942 (SeKatG) in a complex with INH at 2.12‐Å resolution. Three INH molecules were bound to the molecular surface. One INH molecule was bound at the entrance to the ε‐edge side of heme (designated site 1), another was bound at the entrance to the γ‐edge side of heme (site 2), and another was bound to the loop structures in front of the heme propionate side chain (site 3). All of the interactions between KatG and the bound INH seemed to be weak, being mediated mainly by van der Waals contacts. Structural comparisons revealed that the identity and configuration of the residues in site 1 were very similar among SeKatG, Burkholderia pseudomallei KatG, and Mycobacterium tuberculosis KatG. In contrast, sites 2 and 3 were structurally diverse among the three proteins. Thus, site 1 is probably the common KatG INH‐binding site. A static enzymatic analysis and thermal shift assay suggested that the INH‐activating reaction does not proceed in site 1, but rather that this site may function as an initial trapping site for the INH molecule. Database The atomic coordinates and structure factors have been deposited in the Protein Data Bank under the accession number http://www.rcsb.org/pdb/search/structidSearch.do?structureId=3WXO.

Fungus-derived GH-7 family cellobiohydrolase I (CBHI, EC 3.2.1.91) is one of the most important industrial enzymes for cellulosic biomass saccharification. Talaromyces cellulolyticus is well known as a mesophilic fungus producing a high amount of CBHI. Thermostability enhances the economic value of enzymes by making them more robust. However, CBHI has proven difficult to engineer, a fact that stems in part from its low expression in heterozygous hosts and its complex structure. Here, we report the successful improvement of the thermostability of CBHI from T. cellulolyticus using our homologous expression system and protein engineering method. We examined the key structures that seem to contribute to its thermostability using the 3D structural information of CBHI. Some parts of the structure of the Talaromyces emersonii CBHI were grafted into T. cellulolyticus CBHI and thermostable mutant CBHIs were constructed. The thermostability was primarily because of the improvement in the loop structures, and the positive effects of the mutations for thermostability were additive. By combing the mutations, the constructed thermophilic CBHI exhibits high hydrolytic activity toward crystalline cellulose with an optimum temperature at over 70°C. In addition, the strategy can be applied to the construction of the other thermostable CBHIs.

The crystal structure of catalase-peroxidase from Synechococcus elongatus PCC7942 (SeKatG) was solved by molecular replacement and refined to an Rwork of 16.8% and an Rfree of 20.6% at 2.2 Å resolution. The asymmetric unit consisted of only one subunit of the catalase-peroxidase molecule, including a protoporphyrin IX haem moiety and two sodium ions. A typical KatG covalent adduct was formed, Met248-Tyr222-Trp94, which is a key structural element for catalase activity. The crystallographic equivalent subunit was created by a twofold symmetry operation to form the functional dimer. The overall structure of the dimer was quite similar to other KatGs. One sodium ion was located close to the proximal Trp314. The location and configuration of the proximal cation site were very similar to those of typical peroxidases such as ascorbate peroxidase. These features may provide a structural basis for the behaviour of the radical localization/delocalization during the course of the enzymatic reaction.

The archaeal exo-β-d-glucosaminidase (GlmA) is a dimeric enzyme that hydrolyzes chitosan oligosaccharides into monomer glucosamines. GlmA is a member of the glycosidase hydrolase (GH)-A superfamily-subfamily 35 and is a novel enzyme in terms of its primary structure. Here, we present the crystal structure of GlmA in complex with glucosamine at 1.27 Å resolution. The structure reveals that a monomeric form of GlmA shares structural homology with GH42 β-galactosidases, whereas most of the spatial positions of the active site residues are identical to those of GH35 β-galactosidases. We found that upon dimerization, the active site of GlmA changes shape, enhancing its ability to hydrolyze the smaller substrate in a manner similar to that of homotrimeric GH42 β-galactosidase. However, GlmA can differentiate glucosamine from galactose based on one charged residue while using the "evolutionary heritage residue" it shares with GH35 β-galactosidase. Our study suggests that GH35 and GH42 β-galactosidases evolved by exploiting the structural features of GlmA.