XRCC1 codon 399Gln polymorphism is associated with radiotherapy-induced acute dermatitis and mucositis in nasopharyngeal carcinoma patients

BACKGROUND: To evaluate the association between single nucleotide polymorphisms (SNPs) at the 194 and 399 codons of XRCC1, and the risk of severe acute skin and oral mucosa reactions in nasopharyngeal carcinoma patients in China. METHODS: 114 patients with nasopharyngeal carcinoma were sequentially recruited in this study. Heparinized peripheral blood samples were taken for SNPs analysis before the start of radiation treatment. SNPs in XRCC1 (194Arg/Trp and 399Arg/Gln) gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Dermatitis at upper neck and oral mucositis were clinically recorded according to the Common Terminology Criteria for Adverse Events v.3.0. RESULTS: The variant allele frequencies were 0.289 for XRCC1 194Trp and 0.263 for XRCC1 399Gln. Of the 114 patients, 24 experienced grade 3 acute dermatitis and 48 had grade 3 acute mucositis. The XRCC1 399Arg/Gln was significantly associated with the development of grade 3 dermatitis (Odds Ratio, 2.65; 95% CI, 1.04–6.73; p = 0.037, χ2 = 4.357). In addition, it was also associated with higher incidence of grade 3 mucositis with a borderline statistical significance (Odds Ratio, 2.11; 95% CI, 0.951–4.66; p = 0.065, χ2 = 3.411). The relationship between XRCC1 194Arg/Trp and acute dermatitis, and mucositis was not found. CONCLUSIONS: Our investigation shows, for the first time, that patients with the XRCC1 399Arg/Gln genotype were more likely to experience severe acute dermatitis and oral mucositis. With further validation, the information can be used to determine personalized radiotherapy strategy

Changes in bacterial community of soil induced by long-term straw returning

Straw returning is an effective way to improve soil quality. Whether the bacterial community development has been changed by long-term straw returning in non-calcareous soil is not clear. In this study, the following five treatments were administered: soil without fertilizer (CK); wheat and corn straw returning (WC); wheat straw returning with 276 kg N ha−1 yr−1 (WN); manure, 60,000 kg ha−1 pig manure compost (M) and wheat and corn straw returning with 276 kg N ha−1 yr−1 (WCN). The high-throughput 16S rRNA sequencing technology was used to evaluate the bacterial communities. The results showed that the community was composed mostly of two dominant groups (Proteobacteria and Acidobacteria). Bacterial diversity increased after the application of straw and manure. Principal component analyses revealed that the soil bacterial community differed significantly between treatments. The WCN treatment showed relatively higher total soil N, available P, available K, and organic carbon and invertase, urease, cellulase activities and yield than the WC treatment. Our results suggested that application of N fertilizer to straw returning soil had significantly higher soil fertility and enzyme activity than straw returning alone, which resulted in a different bacterial community composition, Stenotrophomonas, Pseudoxanthomonas, and Acinetobacter which were the dominant genera in the WC treatment while Candidatus, Koribacter and Granulicella were the dominant genera in the WCN treatment. To summarize, wheat and maize straw returning with N fertilizer would be the optimum proposal for improving soil quality and yield in the future in non-calcareous fluro-acquic-wheat and maize cultivated soils in the North China Plain in China

Synthesis of carbon-11-labeled 5-HT6R antagonists as new candidate PET radioligands for imaging of Alzheimer’s disease

Carbon-11-labeled serotonin (5-hydroxytryptamine) 6 receptor (5-HT6R) antagonists, 1-[(2-bromophenyl)sulfonyl]-5-[11C]methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole (O-[11C]2a) and 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-[11C]methyl-1-piperazinyl)methyl]-1H-indole (N-[11C]2a), 5-[11C]methoxy-3-((4-methylpiperazin-1-yl)methyl)-1-(phenylsulfonyl)-1H-indole (O-[11C]2b) and 5-methoxy-3-((4-[11C]methylpiperazin-1-yl)methyl)-1-(phenylsulfonyl)-1H-indole (N-[11C]2b), 1-((4-isopropylphenyl)sulfonyl)-5-[11C]methoxy-3-((4-methylpiperazin-1-yl)methyl)-1H-indole (O-[11C]2c) and 1-((4-isopropylphenyl)sulfonyl)-5-methoxy-3-((4-[11C]methylpiperazin-1-yl)methyl)-1H-indole (N-[11C]2c), 1-((4-fluorophenyl)sulfonyl)-5-[11C]methoxy-3-((4-methylpiperazin-1-yl)methyl)-1H-indole (O-[11C]2d) and 1-((4-fluorophenyl)sulfonyl)-5-methoxy-3-((4-[11C]methylpiperazin-1-yl)methyl)-1H-indole (N-[11C]2d), were prepared from their O- or N-desmethylated precursors with [11C]CH3OTf through O- or N-[11C]methylation and isolated by HPLC combined with SPE in 40–50% radiochemical yield, based on [11C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the molar activity (MA) at EOB was 370–740 GBq/μmol with a total synthesis time of ∼40-min from EOB

Synthesis of N-(3-(4-[11C]methylpiperazin-1-yl)−1-(5-methylpyridin-2-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide as a new potential PET agent for imaging of IRAK4 enzyme in neuroinflammation

The reference standard N-(3-(4-methylpiperazin-1-yl)−1-(5-methylpyridin-2-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (9) and its demethylated precursor N-(1-(5-methylpyridin-2-yl)−3-(piperazin-1-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-α]pyrimidine-3-carboxamide (8) were synthesized from pyrazolo[1,5-a]pyrimidine-3-carboxylic acid and ethyl 2-cyanoacetate with overall chemical yield 13% in nine steps and 14% in eight steps, respectively. The target tracer N-(3-(4-[11C]methylpiperazin-1-yl)−1-(5-methylpyridin-2-yl)−1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide ([11C]9) was prepared from its precursor with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with SPE in 50–60% radiochemical yield, based on [11C]CO2 and decay corrected to EOB. The radiochemical purity was >99%, and the specific activity at EOB was 370–1110 GBq/μmol

Complete genome sequencing of Pseudomonas syringae pv. actinidiae Biovar 3, P155, kiwifruit pathogen originating from China

Pseudomonas syringae pv. actinidiae is a bacterial pathogen of kiwifruit. Based on the results of the pathogenicity assay, we sequenced the strain Pseudomonas syringae (Psa3) P155 which possesses a series of virulence and resistance genes, CRISPR candidate elements, prophage related sequences, methylation modifications, genomic islands as well as one plasmid. Most importantly, the copper resistance genes copA, copB, copC, copD, and copZ as well as aminoglycoside resistance gene ksgA were identified in strain P155, which would pose a threat to kiwifruit production. The complete sequence we reported here will provide valuable information for a better understanding of the genetic structure and pathogenic characteristics of the genome of P155

Tracheal intubation in patients with Pierre Robin sequence: development, application, and clinical value based on a 3-dimensional printed simulator

Background: The main clinical manifestations of patients with Pierre Robin sequence (PRS) include micrognathia, the glossoptosis and dyspnoea. The difficulty of tracheal intubation (TI) in such patients is increased.Objective: The purpose of the study was to evaluate the reliability and efficacy of the PRS simulator.Methods: A PRS simulator was developed by using 3-dimensional (3D) printing technology under computer-aided design. A total of 12 anaesthesiologists each trained 5 times for TI on the PRS Training Simulator-1 and recorded the simulation time. After the training, they were randomly divided into three groups with a total of 12 nontrained anaesthesiologists, and the simulation was completed on PRS Simulator-2, 3 and 4. The simulation time was recorded, and the performance was evaluated by three chief anaesthesiologists. Then, all 24 anaesthesiologists completed the questionnaire.Results: A PRS simulator developed by 3D printing was used to simulate the important aspects of TI. The average number of years worked was 6.3 ± 3.1 years, and 66.7% were female. The time for the 12 anaesthesiologists to complete the training gradually decreased (p < 0.01). Compared with the trained anaesthesiologists, the simulation time of TI in the nontrained anaesthesiologists was much longer (all p < 0.01). In addition, the simulation performance of the trained anaesthesiologists was relatively better (all p < 0.01).Conclusion: The reliability and efficacy of the PRS simulator is herein preliminarily validated, and it has potential to become a teaching and training tool for anaesthesiologists