Anaerobic digestion(AD)of waste activated sludge(WAS)is usually limited by the low generation efficiency of methane.Fe(Ⅲ)-loaded chitosan composite(CTS-Fe)have been reported to effectively enhanced the digestion of W...Anaerobic digestion(AD)of waste activated sludge(WAS)is usually limited by the low generation efficiency of methane.Fe(Ⅲ)-loaded chitosan composite(CTS-Fe)have been reported to effectively enhanced the digestion of WAS,but its role in promoting anaerobic sludge digestion remains unclear.In present study,the effects of CTS-Fe on the hydrolysis and methanogenesis stages of WAS anaerobic digestion were investigated.The addition of CTSFe increased methane production potential by 8%-23%under the tested conditions with the addition of 5-20 g/L CTS-Fe.Besides,the results demonstrate that the addition of CTS-Fe could effectively promote the hydrolysis of WAS,evidenced by lower protein or polysaccharides concentration,higher soluble organic carbon in rector adding CTS-Fe,as well as the increased activity of extracellular hydrolase with higher CTS-Fe concentration.Meanwhile,the enrichment of Clostridia abundance(iron-reducing bacteria(IRBs))was observed in CTS-Fe adding reactor(8.9%-13.8%),which was higher than that in the control reactor(7.9%).The observation further suggesting the acceleration of hydrolysis through dissimilatory iron reduction(DIR)process,thus providing abundant substrates for methanogenesis.However,the presence of CTS-Fe was inhibited the acetoclastic and hydrogenotrophic methanogenesis process,which could be ascribed to the Fe(Ⅲ)act as electron acceptor coupled to methane for anaerobic oxidation.Furthermore,coenzyme F420 activity in the CTS-Fe added reactor was 34.9% lower than in the blank,also abundance of microorganisms involved in hydrogenotrophic methanogenesis was decreased.Results from this study could provide theoretical support for the practical applications of CTS-Fe.展开更多
Background:The initial randomized,double-blinded,actively controlled,phase III ANEAS study(NCT03849768)demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal g...Background:The initial randomized,double-blinded,actively controlled,phase III ANEAS study(NCT03849768)demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal growth factor receptor(EGFR)-mutated advanced non-small cell lung cancer(NSCLC).Metastatic disease in the central nervous system(CNS)remains a challenge in the management of NSCLC.This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study.Methods:Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double-blinded fashion.Patients with asymptomatic,stable CNS metastases were included.Follow-up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months,then every 12weeks.CNS responsewas assessed by a neuroradiological blinded,independent central review(neuroradiological-BICR).The primary endpoint for this subgroup analysis was CNS progression-free survival(PFS).Results:Of the 429 patients enrolled and randomized in the ANEAS study,106 patients were found to have CNS metastases(CNS Full Analysis Set,cFAS)at baseline by neuroradiological-BICR,and 60 of them had CNS target lesions(CNS Evaluable for Response,cEFR).Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS(29.0 vs.8.3 months;hazard ratio[HR]=0.31;95%confidence interval[CI],0.17-0.56;P<0.001)and cEFR(29.0 vs.8.3 months;HR=0.26;95%CI,0.11-0.57;P<0.001).The confirmed CNS overall response rate in cEFRwas 85.7%and 75.0%in patients treated with aumolertinib and gefitinib,respectively.Competing risk analysis showed that the estimated probability of CNS progression without prior non-CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNSmetastases at baseline.No new safety findings were observed.Conclusions:These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR-mutated advanced NSCLC with baseline CNS metastases.展开更多
基金supported by the National Natural Science Foundation of China(No.52200031)。
文摘Anaerobic digestion(AD)of waste activated sludge(WAS)is usually limited by the low generation efficiency of methane.Fe(Ⅲ)-loaded chitosan composite(CTS-Fe)have been reported to effectively enhanced the digestion of WAS,but its role in promoting anaerobic sludge digestion remains unclear.In present study,the effects of CTS-Fe on the hydrolysis and methanogenesis stages of WAS anaerobic digestion were investigated.The addition of CTSFe increased methane production potential by 8%-23%under the tested conditions with the addition of 5-20 g/L CTS-Fe.Besides,the results demonstrate that the addition of CTS-Fe could effectively promote the hydrolysis of WAS,evidenced by lower protein or polysaccharides concentration,higher soluble organic carbon in rector adding CTS-Fe,as well as the increased activity of extracellular hydrolase with higher CTS-Fe concentration.Meanwhile,the enrichment of Clostridia abundance(iron-reducing bacteria(IRBs))was observed in CTS-Fe adding reactor(8.9%-13.8%),which was higher than that in the control reactor(7.9%).The observation further suggesting the acceleration of hydrolysis through dissimilatory iron reduction(DIR)process,thus providing abundant substrates for methanogenesis.However,the presence of CTS-Fe was inhibited the acetoclastic and hydrogenotrophic methanogenesis process,which could be ascribed to the Fe(Ⅲ)act as electron acceptor coupled to methane for anaerobic oxidation.Furthermore,coenzyme F420 activity in the CTS-Fe added reactor was 34.9% lower than in the blank,also abundance of microorganisms involved in hydrogenotrophic methanogenesis was decreased.Results from this study could provide theoretical support for the practical applications of CTS-Fe.
基金Hansoh Pharmaceutical Group Co.LtdNational Natural Science Foundation of China,Grant/Award Numbers:82030045,82241227+3 种基金National Multi-disciplinary Treatment Project for Major Diseases,Grant/Award Number:2020NMDTPCollaborative Innovation Center for Clinical and Translational Science by Ministry of Education&Shanghai,Grant/Award Numbers:CCTS-202204,CCTS-202304Shanghai Chest Hospital Basic Research Project,Grant/Award Number:2023YNKT-1Pujiang Program,Grant/Award Number:22PJ1420700。
文摘Background:The initial randomized,double-blinded,actively controlled,phase III ANEAS study(NCT03849768)demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal growth factor receptor(EGFR)-mutated advanced non-small cell lung cancer(NSCLC).Metastatic disease in the central nervous system(CNS)remains a challenge in the management of NSCLC.This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study.Methods:Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double-blinded fashion.Patients with asymptomatic,stable CNS metastases were included.Follow-up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months,then every 12weeks.CNS responsewas assessed by a neuroradiological blinded,independent central review(neuroradiological-BICR).The primary endpoint for this subgroup analysis was CNS progression-free survival(PFS).Results:Of the 429 patients enrolled and randomized in the ANEAS study,106 patients were found to have CNS metastases(CNS Full Analysis Set,cFAS)at baseline by neuroradiological-BICR,and 60 of them had CNS target lesions(CNS Evaluable for Response,cEFR).Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS(29.0 vs.8.3 months;hazard ratio[HR]=0.31;95%confidence interval[CI],0.17-0.56;P<0.001)and cEFR(29.0 vs.8.3 months;HR=0.26;95%CI,0.11-0.57;P<0.001).The confirmed CNS overall response rate in cEFRwas 85.7%and 75.0%in patients treated with aumolertinib and gefitinib,respectively.Competing risk analysis showed that the estimated probability of CNS progression without prior non-CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNSmetastases at baseline.No new safety findings were observed.Conclusions:These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR-mutated advanced NSCLC with baseline CNS metastases.
