Background:Approximately 10%–30%of patients with Hodgkin’s lymphoma(HL)experience relapse or refractory(R/R)disease after first-line standard therapy.Brentuximab vedotin(BV)and immune checkpoint inhibitors(ICIs)have...Background:Approximately 10%–30%of patients with Hodgkin’s lymphoma(HL)experience relapse or refractory(R/R)disease after first-line standard therapy.Brentuximab vedotin(BV)and immune checkpoint inhibitors(ICIs)have important roles in the salvage treatment of R/R HL.However,subsequent treatment for HL refractory to BV and/or ICI treatment is challenging.Methods:We retrospectively analyzed patients in two institutions who had R/R HL,experienced BV or ICI treatment failure,and received radiotherapy(RT)thereafter.The overall response rate(ORR),duration of response(DOR),progression-free survival(PFS),and overall survival(OS)were analyzed.Results:Overall,19 patients were enrolled.First-line systemic therapy comprised doxorubicin,bleomycin,vinblastine,and dacarbazine(ABVD,84.2%);AVD plus ICIs(10.5%);and bleomycin,etoposide,doxorubicin,cyclophosphamide,vincristine,procarbazine,and prednisone(BEACOPP,5.3%).After first-line therapy,15(78.9%)and four patients(21.1%)had refractory disease and relapsed,respectively.After R/R HL diagnosis,six(31.6%),two(10.5%),and 11(57.9%)patients received BV and ICIs concurrently,BV monotherapy,and ICI monotherapy,respectively.All patients received intensity-modulated RT(n=12,63.2%)or volumetric modulated arc therapy(VMAT;n=7,36.8%).The ORR as well as the complete response(CR)rate was 100%;the median DOR to RT was 17.2 months(range,7.9–46.7 months).Two patients showed progression outside the radiation field;one patient had extensive in-field,out-of-field,nodal,and extranodal relapse.With a median follow-up time of 16.2 months(range,9.2–23.2 months),the 1-year PFS and OS were 84.4%and 100%,respectively.PFS was associated with extranodal involvement(P=0.019)and gross tumor volume(P=0.044).All patients tolerated RT well without adverse events of grade≥3.Conclusion:RT is effective and safe for treating HL refractory to BV or ICIs and has the potential to be part of a comprehensive strategy for HL.展开更多
Industrial manufacturing of bioproducts,especially bioethanol,can benefit from high-temperature fermentation,which requires the use of thermotolerant yeast strains.Mitochondrial activity in yeast is closely related to...Industrial manufacturing of bioproducts,especially bioethanol,can benefit from high-temperature fermentation,which requires the use of thermotolerant yeast strains.Mitochondrial activity in yeast is closely related to its over-all metabolism.However,the mitochondrial respiratory changes in response to adaptive thermotolerance are still poorly understood and have been rarely utilized for developing thermotolerant yeast cell factories.Here,adap-tive evolution and transcriptional sequencing,as well as whole-genome-level gene knockout,were used to obtain a thermotolerant strain of Saccharomyces cerevisiae.Furthermore,thermotolerance and bioethanol production efficiency of the engineered strain were examined.Physiological evaluation showed the boosted fermentation ca-pacity and suppressed mitochondrial respiratory activity in the thermotolerant strain.The improved fermentation produced an increased supply of adenosine triphosphate required for more active energy-consuming pathways.Transcriptome analysis revealed significant changes in the expression of the genes involved in the mitochondrial respiratory chain.Evaluation of mitochondria-associated gene knockout confirmed that ADK1,DOC1,or MET7 were the key factors for the adaptive evolution of thermotolerance in the engineered yeast strain.Intriguingly,overexpression of DOC1 with TEF1 promoter regulation led to a 10.1%increase in ethanol production at 42℃.The relationships between thermotolerance,mitochondrial activity,and respiration were explored,and a ther-motolerant yeast strain was developed by altering the expression of mitochondrial respiration-related genes.This study provides a better understanding on the physiological mechanism of adaptive evolution of thermotolerance in yeast.展开更多
The Dashuigou Te deposit is a unique independent one found in the world, and hosted in the plagioclase amphibolite. The upper intercept age of single zircon from the amphibolite can be considered to be the crystalliza...The Dashuigou Te deposit is a unique independent one found in the world, and hosted in the plagioclase amphibolite. The upper intercept age of single zircon from the amphibolite can be considered to be the crystallization age of the source-rock of the amphibolite (tholeiitic basalt), while the lower intercept is nearly consistent with the time of the tectono-thermal event.展开更多
基金supported by grants from the Major Scientific Research Program for Young and Middle-aged Health Professionals of Fujian Province,China(grant number:2022ZQNZD002)the Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors(Fujian Medical University)and Clinical Research Center for Radiology and Radiotherapy of Fujian Province(Digestive,Hematological and Breast Malignancies).
文摘Background:Approximately 10%–30%of patients with Hodgkin’s lymphoma(HL)experience relapse or refractory(R/R)disease after first-line standard therapy.Brentuximab vedotin(BV)and immune checkpoint inhibitors(ICIs)have important roles in the salvage treatment of R/R HL.However,subsequent treatment for HL refractory to BV and/or ICI treatment is challenging.Methods:We retrospectively analyzed patients in two institutions who had R/R HL,experienced BV or ICI treatment failure,and received radiotherapy(RT)thereafter.The overall response rate(ORR),duration of response(DOR),progression-free survival(PFS),and overall survival(OS)were analyzed.Results:Overall,19 patients were enrolled.First-line systemic therapy comprised doxorubicin,bleomycin,vinblastine,and dacarbazine(ABVD,84.2%);AVD plus ICIs(10.5%);and bleomycin,etoposide,doxorubicin,cyclophosphamide,vincristine,procarbazine,and prednisone(BEACOPP,5.3%).After first-line therapy,15(78.9%)and four patients(21.1%)had refractory disease and relapsed,respectively.After R/R HL diagnosis,six(31.6%),two(10.5%),and 11(57.9%)patients received BV and ICIs concurrently,BV monotherapy,and ICI monotherapy,respectively.All patients received intensity-modulated RT(n=12,63.2%)or volumetric modulated arc therapy(VMAT;n=7,36.8%).The ORR as well as the complete response(CR)rate was 100%;the median DOR to RT was 17.2 months(range,7.9–46.7 months).Two patients showed progression outside the radiation field;one patient had extensive in-field,out-of-field,nodal,and extranodal relapse.With a median follow-up time of 16.2 months(range,9.2–23.2 months),the 1-year PFS and OS were 84.4%and 100%,respectively.PFS was associated with extranodal involvement(P=0.019)and gross tumor volume(P=0.044).All patients tolerated RT well without adverse events of grade≥3.Conclusion:RT is effective and safe for treating HL refractory to BV or ICIs and has the potential to be part of a comprehensive strategy for HL.
基金supported by the National Key Research and De-velopment Program of China (2021YFC2103300),Research Equipment Program of Chinese Academy of Sciences (YJKYYQ20170023)National Natural Science Foundation of China (32071423,31470214,and 32200067)+1 种基金Natural Science Foundation of Hebei Province (C2020204013)Development Program Projects of Hebei Province (22322905D).
文摘Industrial manufacturing of bioproducts,especially bioethanol,can benefit from high-temperature fermentation,which requires the use of thermotolerant yeast strains.Mitochondrial activity in yeast is closely related to its over-all metabolism.However,the mitochondrial respiratory changes in response to adaptive thermotolerance are still poorly understood and have been rarely utilized for developing thermotolerant yeast cell factories.Here,adap-tive evolution and transcriptional sequencing,as well as whole-genome-level gene knockout,were used to obtain a thermotolerant strain of Saccharomyces cerevisiae.Furthermore,thermotolerance and bioethanol production efficiency of the engineered strain were examined.Physiological evaluation showed the boosted fermentation ca-pacity and suppressed mitochondrial respiratory activity in the thermotolerant strain.The improved fermentation produced an increased supply of adenosine triphosphate required for more active energy-consuming pathways.Transcriptome analysis revealed significant changes in the expression of the genes involved in the mitochondrial respiratory chain.Evaluation of mitochondria-associated gene knockout confirmed that ADK1,DOC1,or MET7 were the key factors for the adaptive evolution of thermotolerance in the engineered yeast strain.Intriguingly,overexpression of DOC1 with TEF1 promoter regulation led to a 10.1%increase in ethanol production at 42℃.The relationships between thermotolerance,mitochondrial activity,and respiration were explored,and a ther-motolerant yeast strain was developed by altering the expression of mitochondrial respiration-related genes.This study provides a better understanding on the physiological mechanism of adaptive evolution of thermotolerance in yeast.
文摘The Dashuigou Te deposit is a unique independent one found in the world, and hosted in the plagioclase amphibolite. The upper intercept age of single zircon from the amphibolite can be considered to be the crystallization age of the source-rock of the amphibolite (tholeiitic basalt), while the lower intercept is nearly consistent with the time of the tectono-thermal event.
