The physiological function for thiaminase II, a thiamin-degrading enzyme, has eluded investigators for more than 50 years. Here, we demonstrate that this enzyme is involved in the regeneration of the thiamin pyrimidine rather than in thiamin degradation, and we identify a new pathway involved in the salvage of base-degraded forms of thiamin. This pathway is widely distributed among bacteria, archaea and eukaryotes. In this pathway, thiamin hydrolysis products such as N-formyl-4-amino-5-aminomethyl-2-methylpyrimidine (formylaminopyrimidine; 15) are transported into the cell using the ThiXYZ transport system, deformylated by the ylmB-encoded amidohydrolase and hydrolyzed to 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP; 6)-an intermediate on the de novo thiamin biosynthetic pathway. To our knowledge this is the first example of a thiamin salvage pathway involving thiamin analogs generated by degradation of one of the heterocyclic rings of the cofactor.
SUMMARY Olfactory receptors (ORs) form a large family of G-protein coupled receptor proteins (GPCRs) responsible for sensing the ambient chemical environment. The molecular recognition strategies used by ORs to detect and distinguish odorant molecules are unclear. Here, we investigated the variable of odorant carbon chain conformation for an established odorant-OR pair: n-octanal and rat OR-I7. A series of conformationally restricted octanal mimics were tested on live olfactory sensory neurons (OSNs). Our results support a model in which unactivated OR-I7 binds aliphatic aldehydes indiscriminately, and then applies conformational and length filters to distinguish agonists from antagonists. Specific conformers are proposed to activate OR-I7 by steric buttressing of an OR activation pocket. Probing endogenously expressed rat OSNs with octanal and constrained mimics furnished evidence that odorant conformation contributes to an odorant’s unique olfactory code signature.
Background It remains no clear conclusion about which is better between robot-assisted thoracic surgery (RATS) and video-assisted thoracic surgery (VATS) for the treatment of patients with non-small cell lung cancer (NSCLC). Therefore, this meta-analysis aimed to compare the short-term and long-term efficacy between RATS and VATS for NSCLC. Methods Pubmed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Medline, and Web of Science databases were comprehensively searched for studies published before December 2020. The quality of the articles was evaluated using the Newcastle-Ottawa Scale (NOS) and the data analyzed using the Review Manager 5.3 software. Fixed or random effect models were applied according to heterogeneity. Subgroup analysis and sensitivity analysis were conducted. Results A total of 18 studies including 11,247 patients were included in the meta-analyses, of which 5114 patients were in the RATS group and 6133 in the VATS group. Compared with VATS, RATS was associated with less blood loss (WMD = − 50.40, 95% CI -90.32 ~ − 10.48, P = 0.010), lower conversion rate (OR = 0.50, 95% CI 0.43 ~ 0.60, P < 0.001), more harvested lymph nodes (WMD = 1.72, 95% CI 0.63 ~ 2.81, P = 0.002) and stations (WMD = 0.51, 95% CI 0.15 ~ 0.86, P = 0.005), shorter duration of postoperative chest tube drainage (WMD = − 0.61, 95% CI -0.78 ~ − 0.44, P < 0.001) and hospital stay (WMD = − 1.12, 95% CI -1.58 ~ − 0.66, P < 0.001), lower overall complication rate (OR = 0.90, 95% CI 0.83 ~ 0.99, P = 0.020), lower recurrence rate (OR = 0.51, 95% CI 0.36 ~ 0.72, P < 0.001), and higher cost (WMD = 3909.87 USD, 95% CI 3706.90 ~ 4112.84, P < 0.001). There was no significant difference between RATS and VATS in operative time, mortality, overall survival (OS), and disease-free survival (DFS). Sensitivity analysis showed that no significant differences were found between the two techniques in conversion rate, number of harvested lymph nodes and stations, and overall complication. Conclusions The results revealed that RATS is a feasible and safe technique compared with VATS in terms of short-term and long-term outcomes. Moreover, more randomized controlled trials comparing the two techniques with rigorous study designs are still essential to evaluate the value of robotic surgery for NSCLC.
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