Postoperative chemoradiotherapy with capecitabine and oxaliplatin vs.capecitabine for pathological stage N2 rectal cancer

Objective:Several studies have been conducted on the effects and toxicity of adding oxaliplatin to fluorouracilbased or capecitabine-based chemoradiotherapy(CRT)regimens as significantly increasing the toxic response without benefit to survival.In this study,we further explored the role of these two postoperative CRT regimens in patients with pathological stage N2 rectal cancer.Methods:This study was a subgroup analysis of a randomized clinical trial.A total of 180 patients with pathological stage N2 rectal cancer were eligible,85 received capecitabine with radiotherapy(RT),and 95 received capecitabine and oxaliplatin with RT.Patients in both groups received adjuvant chemotherapy[capecitabine and oxaliplatin(XELOX);or fluorouracil,leucovorin,and oxaliplatin(FOLFOX)]after CRT.Results:At a median follow-up of 59.2[interquartile range(IQR),34.0−96.8]months,the three-year diseasefree survival(DFS)was 53.3%and 64.9%in the control group and the experimental group,respectively[hazard ratio(HR),0.63;95%confidence interval(95%CI),0.41−0.98;P=0.04].There was no significant difference between the groups in overall survival(OS)(HR,0.62;95%CI,0.37−1.05;P=0.07),the incidence of locoregional recurrence(HR,0.62;95%CI,0.24−1.64;P=0.33),the incidence of distant metastasis(HR,0.67;95%CI,0.42−1.06;P=0.09)and grade 3−4 acute toxicities(P=0.78).For patients with survival longer than 3 years,the conditional overall survival(COS)was significantly better in the experimental group(HR,0.39;95%CI,0.16−0.96;P=0.03).Conclusions:Our results indicated that adding oxaliplatin to capecitabine-based postoperative CRT is safe and effective in patients with pathological stage N2 rectal cancer.

Genetic polymorphisms in genes regulating cell death and prognosis of patients with rectal cancer receiving postoperative chemoradiotherapy

Objective:The identification of biomarkers for predicting chemoradiotherapy efficacy is essential to optimize personalized treatment.This study determined the effects of genetic variations in genes involved in apoptosis,pyroptosis,and ferroptosis on the prognosis of patients with locally advanced rectal cancer receiving postoperative chemoradiotherapy(CRT).Methods:The Sequenom MassARRAY was used to detect 217 genetic variations in 40 genes from 300 patients with rectal cancer who received postoperative CRT.The associations between genetic variations and overall survival(OS)were evaluated using hazard ratios(HRs)and 95%confidence intervals(CIs)computed using a Cox proportional regression model.Functional experiments were performed to determine the functions of the arachidonate 5-lipoxygenase(ALOX5)gene and the ALOX5 rs702365 variant.Results:We detected 16 genetic polymorphisms in CASP3,CASP7,TRAILR2,GSDME,CASP4,HO-1,ALOX5,GPX4,and NRF2 that were significantly associated with OS in the additive model(P<0.05).There was a substantial cumulative effect of three genetic polymorphisms(CASP4 rs571407,ALOX5 rs2242332,and HO-1 rs17883419)on OS.Genetic variations in the CASP4 and ALOX5 gene haplotypes were associated with a higher OS.We demonstrated,for the first time,that rs702365[G]>[C]represses ALOX5 transcription and corollary experiments suggested that ALOX5 may promote colon cancer cell growth by mediating an inflammatory response.Conclusions:Polymorphisms in genes regulating cell death may play essential roles in the prognosis of patients with rectal cancer who are treated with postoperative CRT and may serve as potential genetic biomarkers for individualized treatment.

Organophosphine ligand derived sandwich-structural electrocatalyst for oxygen evolution reaction

The synchronous construction of metal phosphate and phosphorus-doped carbon structures is of great significance to innovate the design,synthesis,and application of catalysts,as these phosphoruscontaining composite materials have shown a remarkable contribution to electrocatalysts.However,their preparation procedure generally involves using large amounts of excess phosphorus sources for phosphorization,which inevitably release poisonous PH_(3) or dangerous phosphorus vapor.Here,a strategy for in-situ formation of FePO_(4) embedded in P-doped carbon 2D nano film(FePO_(4)/PdC)is developed using a highly integrated precursor,which is a small molecular organophosphine ligand,1,1’bis(diphenylphosphine)ferrocene(DPPF).The multi-source precursor DPPF that contains Fe,P,and C is molecular-vapor-deposited on the nickel foam(NF)supported ZIF-67 nanosheets to obtain the composite catalyst,namely DPPF-500/ZIF-67/NF.FePO_(4)/PdC encapsulated the ZIF-67 derived Co/N-doped carbon matrix(Co NC)to form a sandwich structure FePO_(4)/PdC@CoNC.The constructed catalyst shows good performance for OER,requiring an overpotential of only 297 m V to deliver 600 m A/cm^(2) with a Tafel slope of 42.7 m V dec^(-1).DFT calculations demonstrate that the synergistic effects between the metal active center and P-doped carbon film reduce the energy barriers and improve electron transport.This method of constructing P-containing catalysts overcomes the demand for additional P sources to realize eco-friendly fabrication and yields a unique structure with good catalytic activity.

十字花科黑腐病菌Ⅲ型效应物XopXccR1植物亚细胞定位

【目的】植物病原细菌通过Ⅲ型分泌系统(type Ⅲ secretion system,T3SS)将Ⅲ型效应物(type Ⅲ secreted effectors,T3SEs)分泌转运到宿主细胞的不同位点上,进而行使不同的致病功能。本研究旨在确定Xcc 8004 Ⅲ型效应物中分子量最大的蛋白XopXccR1在植物中的亚细胞定位。【方法】利用生物信息学方法分析XopXccR1的跨膜信息。通过同源重组方法将XopXccR1全长、N端(1–1220aa)和C端(1221–2030 aa)分别克隆到植物表达载体pCAMBIA-2300-35S::EGFP上,利用根癌农杆菌介导的瞬时表达浸染本生烟,通过激光共聚焦显微镜观察亚细胞定位结果。【结果】XopXccR1全长和N端定位在本生烟细胞膜上,而C端定位在细胞质中。【结论】XopXccR1的N端与C端可能分别存在定位信号,N端信号主导全长蛋白的最终定位。