In this work,an effective catalyst of Cu/MnOOH has been successfully constructed for electrochemical nitrate reduction reaction(e NO_(3)RR)for synthesis of ammonia(NH_(3))under ambient conditions.The substrate of MnOO...In this work,an effective catalyst of Cu/MnOOH has been successfully constructed for electrochemical nitrate reduction reaction(e NO_(3)RR)for synthesis of ammonia(NH_(3))under ambient conditions.The substrate of MnOOH plays an important role on the size and electronic structure of Cu nanoparticles,where Cu has the ultrafine size of 2.2 nm and positive shift of its valence states,which in turn causes the increased number of Cu active sites and enhanced intrinsic activity of every active site.As a result,this catalyst realizes an excellent catalytic performance on eNO_(3)RR with the maximal NH_(3)Faraday efficiency(FE)(96.8%)and the highest yield rate(55.51 mg h^(-1)cm^(-2))at a large NH_(3)partial current density of700 m A/cm^(2),which could help to promote the industrialization of NH_(3)production under ambient conditions.展开更多
Elevated collagen levels within breast tumors are strongly associated with tumor progression and present a barrier to effective therapeutic agent penetration within the tumor microenvironment(TME),leading to poor clin...Elevated collagen levels within breast tumors are strongly associated with tumor progression and present a barrier to effective therapeutic agent penetration within the tumor microenvironment(TME),leading to poor clinical outcomes.To address this challenge,we engineered a probiotic strain to degrade collagen within the TME by selectively colonizing in tumors and releasing bacterial collagenase in a lysis-dependent manner.Initially,we constructed a therapeutic bacterial strain designed to lyse within the TME and release an encoded immunotoxin comprising a nanobody targeting CD47(CD47nb)and a modified Pseudomonas exotoxin A(PE38KDEL).The introduction of collagenase-expressing bacteria,in conjunction with therapeutic immunotoxin,reduced collagen fiber levels within the TME,resulting in inhibited tumor growth and prolonged survival in a murine model of breast cancer.Furthermore,we investigated the broader applicability of the collagenase-expressing bacterial strain in combination with chemotherapeutic drugs,such as doxorubicin.Remarkably,synergistic antitumor effects were observed in mice treated with this combination therapy.In conclusion,our study demonstrates that probiotic delivery of bacterial collagenase offers a promising adjuvant treatment strategy for selectively degrading intratumoral collagen,thereby improving the efficacy of anticancer therapies in breast cancer.展开更多
This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive(N)and nivolumab–chemotherapy(N/C)combinations based on PD-L1 expression.Eligible patients exhibited resec...This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive(N)and nivolumab–chemotherapy(N/C)combinations based on PD-L1 expression.Eligible patients exhibited resectable clinical stage IIA–IIIB(AJCC 8th edition)NSCLC without EGFR/ALK alterations.Patients received either mono-nivolumab(N)or nivolumab+nabpaclitaxel+carboplatin(N/C)for three cycles based on PD-L1 expression.The primary endpoint was the major pathological response(MPR).Key secondary endpoints included the pathologic complete response(pCR),objective response rate(ORR),and event-free survival(EFS).Baseline PD-L1 expression and perioperative circulating tumor DNA(ctDNA)status were correlated with pCR and EFS.Fifty-two patients were enrolled,with 46 undergoing surgeries.The MPR was 50.0%(26/52),with 25.0%(13/52)achieving pCR,and 16.7%and 66.7%for patients with PD-L1≥50%in N and N/C groups,respectively.Thirteen(25.0%)patients experienced grade 3 or higher immune-related adverse events during neoadjuvant treatment.Patients with post-neoadjuvant ctDNA negativity was more likely to have pCR(39.1%)compared with those remained positive(6.7%,odds ratio=6.14,95%CI 0.84-Inf,p=0.077).With a median follow-up of 25.1 months,the 18-month EFS rate was 64.8%(95%CI 51.9–81.0%).For patients with ctDNA–vs.ctDNA+,the 18m-EFS rate was 93.8%vs 47.3%(HR,0.15;95%CI 0.04,0.94;p=0.005).Immunochemotherapy may serve as an optimal neoadjuvant treatment even for patients with PD-L1 expression≥50%.ctDNA negativity following neoadjuvant treatment and surgery could help identify superior pathological and survival benefits,which requires further confirmation in a prospective clinical trial(NCT04015778).展开更多
基金supported in part by National Natural Science Foundation of China(No.51925102)National Key R&D Program of China(No.2022YFA1504101)。
文摘In this work,an effective catalyst of Cu/MnOOH has been successfully constructed for electrochemical nitrate reduction reaction(e NO_(3)RR)for synthesis of ammonia(NH_(3))under ambient conditions.The substrate of MnOOH plays an important role on the size and electronic structure of Cu nanoparticles,where Cu has the ultrafine size of 2.2 nm and positive shift of its valence states,which in turn causes the increased number of Cu active sites and enhanced intrinsic activity of every active site.As a result,this catalyst realizes an excellent catalytic performance on eNO_(3)RR with the maximal NH_(3)Faraday efficiency(FE)(96.8%)and the highest yield rate(55.51 mg h^(-1)cm^(-2))at a large NH_(3)partial current density of700 m A/cm^(2),which could help to promote the industrialization of NH_(3)production under ambient conditions.
基金sponsored by the National Natural Science Founda-tion of China(22134003)the National Key Research and Develop-ment Program of China(2020YFA0908800).
文摘Elevated collagen levels within breast tumors are strongly associated with tumor progression and present a barrier to effective therapeutic agent penetration within the tumor microenvironment(TME),leading to poor clinical outcomes.To address this challenge,we engineered a probiotic strain to degrade collagen within the TME by selectively colonizing in tumors and releasing bacterial collagenase in a lysis-dependent manner.Initially,we constructed a therapeutic bacterial strain designed to lyse within the TME and release an encoded immunotoxin comprising a nanobody targeting CD47(CD47nb)and a modified Pseudomonas exotoxin A(PE38KDEL).The introduction of collagenase-expressing bacteria,in conjunction with therapeutic immunotoxin,reduced collagen fiber levels within the TME,resulting in inhibited tumor growth and prolonged survival in a murine model of breast cancer.Furthermore,we investigated the broader applicability of the collagenase-expressing bacterial strain in combination with chemotherapeutic drugs,such as doxorubicin.Remarkably,synergistic antitumor effects were observed in mice treated with this combination therapy.In conclusion,our study demonstrates that probiotic delivery of bacterial collagenase offers a promising adjuvant treatment strategy for selectively degrading intratumoral collagen,thereby improving the efficacy of anticancer therapies in breast cancer.
基金supported by the Bristol Myers Squibb(grant number BMSCA209-8D8)the Chinese Thoracic Oncology Group(CTONG1804)ctDNA analysis was performed by Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis and the Berry Oncology Corporation without compensation.
文摘This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive(N)and nivolumab–chemotherapy(N/C)combinations based on PD-L1 expression.Eligible patients exhibited resectable clinical stage IIA–IIIB(AJCC 8th edition)NSCLC without EGFR/ALK alterations.Patients received either mono-nivolumab(N)or nivolumab+nabpaclitaxel+carboplatin(N/C)for three cycles based on PD-L1 expression.The primary endpoint was the major pathological response(MPR).Key secondary endpoints included the pathologic complete response(pCR),objective response rate(ORR),and event-free survival(EFS).Baseline PD-L1 expression and perioperative circulating tumor DNA(ctDNA)status were correlated with pCR and EFS.Fifty-two patients were enrolled,with 46 undergoing surgeries.The MPR was 50.0%(26/52),with 25.0%(13/52)achieving pCR,and 16.7%and 66.7%for patients with PD-L1≥50%in N and N/C groups,respectively.Thirteen(25.0%)patients experienced grade 3 or higher immune-related adverse events during neoadjuvant treatment.Patients with post-neoadjuvant ctDNA negativity was more likely to have pCR(39.1%)compared with those remained positive(6.7%,odds ratio=6.14,95%CI 0.84-Inf,p=0.077).With a median follow-up of 25.1 months,the 18-month EFS rate was 64.8%(95%CI 51.9–81.0%).For patients with ctDNA–vs.ctDNA+,the 18m-EFS rate was 93.8%vs 47.3%(HR,0.15;95%CI 0.04,0.94;p=0.005).Immunochemotherapy may serve as an optimal neoadjuvant treatment even for patients with PD-L1 expression≥50%.ctDNA negativity following neoadjuvant treatment and surgery could help identify superior pathological and survival benefits,which requires further confirmation in a prospective clinical trial(NCT04015778).
