Information steganography has received more and more attention from scholars nowadays,especially in the area of image steganography,which uses image content to transmit information and makes the existence of secret in...Information steganography has received more and more attention from scholars nowadays,especially in the area of image steganography,which uses image content to transmit information and makes the existence of secret information undetectable.To enhance concealment and security,the Steganography without Embedding(SWE)method has proven effective in avoiding image distortion resulting from cover modification.In this paper,a novel encrypted communication scheme for image SWE is proposed.It reconstructs the image into a multi-linked list structure consisting of numerous nodes,where each pixel is transformed into a single node with data and pointer domains.By employing a special addressing algorithm,the optimal linked list corresponding to the secret information can be identified.The receiver can restore the secretmessage fromthe received image using only the list header position information.The scheme is based on the concept of coverless steganography,eliminating the need for any modifications to the cover image.It boasts high concealment and security,along with a complete message restoration rate,making it resistant to steganalysis.Furthermore,this paper proposes linked-list construction schemeswithin theproposedframework,which caneffectively resist a variety of attacks,includingnoise attacks and image compression,demonstrating a certain degree of robustness.To validate the proposed framework,practical tests and comparisons are conducted using multiple datasets.The results affirm the framework’s commendable performance in terms of message reduction rate,hidden writing capacity,and robustness against diverse attacks.展开更多
Objective: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. The prognostic factor currently used is not accurate enough to predict the outcomes of patients with DLBCL. The prognostic significance o...Objective: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. The prognostic factor currently used is not accurate enough to predict the outcomes of patients with DLBCL. The prognostic significance of interim PET/CT in DLBCL remains controversial. The aim of this study is to determine the predictive value of interim 18F-FDG PET/CT after first-line treatment in patients with DLBCL. Methods: Thirty-two patients with DLBCL underwent baseline, interim and post-treatment lSF-FDG PET/CT scans. Imaging results were analyzed for the survival of patients via software SPSS 13.0, retrospectively. Results: Thirty-one of the 32 patients were treated with R-CHOP regimen, and interim 18F-FDG PET/CT of 24 patients was performed after 2 cycles of treatment. After a median follow-up period of 16.7 months, the 2-year progression-free survival (PFS) rates were significantly different between the groups above and below SUVmax CUt-Off value of 2.5 (P=0.039). No significant differences were found in the 2-year PFS rates if SUVm, cut-offvalues were set as 2.0 and 3.0, respectively (P=0.360; P=0.113). Conclusions: Interim PET/CT could predict the prognosis of DLBCL patients with the SUVmax cut-off value of 2.5, but more clinical data should be concluded to confirm this conclusion.展开更多
Objective: High-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT) is the standard of care in the upfront or relapsed/refractory setting in some patients with non-Hodgkin lymphoma (...Objective: High-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT) is the standard of care in the upfront or relapsed/refractory setting in some patients with non-Hodgkin lymphoma (NHL). However, a proportion of patients do not respond to ASCT. lSF-fluorodeoxyglueose (FDG) positron emission tomography (PET)/computed tomography (CT) has been widely used for staging, response evaluation, and prognosis prediction. Here, we investigated the prognostic role of PET/CT in NHL patients before and after ASCT. Methods: A retrospective study was conducted at Peking University Cancer Hospital. All NHL patients who underwent ASCT between March 2010 and July 2016 were identified. Patients who had PET/CT scan before and after ASCT were included. Deauville criteria (5-point scale) were used to interpret PET scans. Univariate and multivariate survival analyses were performed using Cox regression. The predictive value of PET scanning was estimated by comparing the area under the receiver operating characteristic (ROC) curve. Results: In total, 79 patients were enrolled in this study. In univariate analysis, pre- and post-ASCT PET result was identified as prognostic factors for 3-year progression-free survival (PFS) and overall survival (OS). Patients with negative pre-ASCT PET result demonstrated significantly better PFS (84.2% vs. 54.2%) and OS (89.2% vs. 63.6%) than patients with positive pre-ASCT PET result. PFS (91.6% vs. 25.3%) and OS (96.5% vs. 36.8%) were also significantly different between patients with negative and positive post-ASCT PET result. Multivariate analysis also showed a significant association between survival and post-ASCT PET result. ROC analysis revealed that the predictive value of post-ASCT PET result was superior to that of pre-ASCT PET result alone. Combined pre- and post-ASCT PET result is better for predicting outcomes in patients with NHL receiving transplantation. Deauville criteria score 〉3 was identified as the best cutoffvalue for post-ASCT PET. Conclusions: Post-ASCT PET result was more important than pre-ASCT PET result in predicting outcomes for NHL patients who underwent ASCT. The prognostic significance can be improved when combining pre- ASCT PET result with post-ASCT PET result. Deauville criteria can be used for interpreting PET scans in this scenario.展开更多
The interprovincial trade embodied carbon emissions plays an important role in the national emission reduction target among China's provinces. Furthermore, it will affect the smooth start-up of the national carbon...The interprovincial trade embodied carbon emissions plays an important role in the national emission reduction target among China's provinces. Furthermore, it will affect the smooth start-up of the national carbon trade market as well as the implementation of targets in 2030 for dealing with the climate change. Based on constructed MRIO model, this paper analyzes the embodied carbon emission trade flows among Beijing, Tianjin, Hebei and surrounding regions such as Shanxi, Shaanxi, and Inner Mongolia. The results indicate that six provinces have formed different patterns of carbon trade balance, where Beijing, Tianjin, and Hebei provinces are in a deficit position, while the other three provinces are in a surplus position.Beijing, Tianjin, and Hebei have transferred part of the carbon emissions to the other three provinces, which shows greater heterogeneity among various provinces and provincial different sectors. On basis of the conclusions, this paper puts forward some suggestions on provincial decomposition, responsibility distribution, and provincial collaborative reduction for national emission reduction targets.展开更多
Objective: High-dose chemotherapy(HDC) followed by autologous hematopoietic stem cell transplantation(auto-HSCT) plays an important role in improving outcomes of diffuse large B cell lymphoma(DLBCL) patients.18 F-fluo...Objective: High-dose chemotherapy(HDC) followed by autologous hematopoietic stem cell transplantation(auto-HSCT) plays an important role in improving outcomes of diffuse large B cell lymphoma(DLBCL) patients.18 F-fluorodeoxyglucose(18 F-FDG) positron emission tomography(PET)/computed tomography(CT) has been widely accepted in response assessment and prediction of prognosis in DLBCL. Here, we report the value of 18 FFDG PET/CT pre-and post-HSCT in predicting outcomes of patients with DLBCL.Methods: DLBCL patients who had PET/CT scan before and after HSCT were included. PET results were interpreted based upon Deauville criteria. The prognostic value of 18 F-FDG PET/CT in auto-HSCT was evaluated.Results: Eighty-four patients were enrolled. In univariate analysis, pre-and post-HSCT PET findings were correlated with 3-year progression-free survival(PFS) [hazard ratio(HR)=4.391, P=0.001; HR=7.607, P<0.001] and overall survival(OS)(HR=4.792, P=0.008; HR=26.138, P<0.001). Patients receiving upfront auto-HSCT after firstline treatment had better outcomes than relapsed/refractory DLBCL patients(3-year PFS, P<0.001; 3-year OS,P<0.001). In the relapsed/refractory patients, pre-and post-HSCT PET findings were also associated with 3-year PFS(P=0.003 vs. P<0.001) and OS(P=0.027 vs. P<0.001). A significant correlation was observed between clinical response to chemotherapy before auto-HSCT and outcomes of patients in the entire cohort(3-year PFS, P<0.001;3-year OS, P<0.001) and in the subgroup of 21 patients with positive pre-HSCT PET(3-year PFS, P=0.084; 3-year OS, P=0.240). A significant association between survival and post-HSCT PET findings was observed in multivariate analysis(HR=5.168, P<0.001).Conclusions: PET results before and after HSCT are useful prognostic factors for DLBCL patients receiving HSCT. Patients who responded to chemotherapy, even those with positive pre-HSCT PET, are appropriate candidates for auto-HSCT.展开更多
Objective: Although L-asparaginase(L-ASP) is a standard treatment for lymphoblastic lymphoma(LBL),hypersensitivity reactions by some patients limit its application. Polyethylene glycol-conjugated asparaginase(PE...Objective: Although L-asparaginase(L-ASP) is a standard treatment for lymphoblastic lymphoma(LBL),hypersensitivity reactions by some patients limit its application. Polyethylene glycol-conjugated asparaginase(PEGASP) has a lower immunogenicity and is a standard treatment in all pediatric acute lymphoblastic leukemia(ALL).In this study, we investigated the efficacy and toxicity of PEG-ASP instead of L-ASP as used in the BFM-90regimen(PEG-ASP-BFM-90) for adult LBL.Methods: Between June 2012 and July 2015, we treated 30 adult patients with newly diagnosed LBL, using PEGASP-BFM-90 in a prospective, multicenter and single-arm clinical study at 5 participating institutions in China.Results: All the 30 patients, including 19 males and 11 females with a median age of 30(range: 18–62) years,completed 128 times of the PEG-ASP, with the median of 4(range: 2–6) times. Patients did not receive radiotherapy at this time. The overall response rate was 86.7%(26/30), with 50.0%(15/30) complete response and36.7%(11/30) partial response. The 3-year overall survival was 46.0% [95% confidence interval(95% CI),28.2%–64.8%], and the 3-year progression-free survival was 43.0%(95% CI, 25.7%–62.0%). Major adverse events were myelosuppression, reduced fibrinogen, liver dysfunction and digestive tract toxicities. No allergic reaction and no treatment-related mortality or severe complications were recorded.Conclusions: Our clinical data and observed outcomes indicate that 1 dose of PEG-ASP can replace multiple doses of native L-ASP in BFM-90, with predominantly grade 3–4 neutropenia for adult LBL, and no therapyrelated deaths. The effect is similar to previous reports of PEG-ASP-containing regimens for adult ALL. Major advantages include less serious allergic reactions, 2–3 weeks of action duration, and convenience for patients and physicians.展开更多
Objective:Previous studies reported that 4-1BB-based CD19 chimeric antigen receptor(CAR)-T cells were more beneficial for the clinical outcomes than CD28-based CAR-T cells,especially the lower incidence rate of severe...Objective:Previous studies reported that 4-1BB-based CD19 chimeric antigen receptor(CAR)-T cells were more beneficial for the clinical outcomes than CD28-based CAR-T cells,especially the lower incidence rate of severe adverse events.However,the median progression-free survival(mPFS)of 4-1BB-based product Kymriah was shorter than that of CD28-based Yescarta(2.9 months vs.5.9 months),suggesting that Kymriah was limited in the long-term efficacy.Thus,a safe and durable 4-1BB-based CD19 CAR-T needs to be developed.Methods:We designed a CD19-targeted CAR-T(named as IM19)which consisted of an FMC63 scFv,4-1BB and CD3ζintracellular domain and was manufactured into a memory T-enriched formulation.A phase I/II clinical trial was launched to evaluate the clinical outcomes of IM19 in relapsed or refractory(r/r)B cell non-Hodgkin lymphoma(B-NHL).Dose-escalation investigation(at a dose of 5×10^(5)/kg,1×10^(6)/kg and 3×106/kg)was performed in 22 r/r B-NHL patients.All patients received a single infusion of IM19 after 3-day conditional regimen.Results:At month 3,the overall response rate(ORR)was 59.1%,the complete response rate(CRR)was 50.0%.The mPFS was 6 months and the 1-year overall survival rate was 77.8%.Cytokine release syndrome(CRS)occurred in 13 patients(59.1%),with 54.5%of grade 1−2 CRS.Only one patient(4.5%)experienced grade 3 CRS and grade 3 neurotoxicity.Conclusions:These results demonstrated the safety and durable efficacy of a 4-1BB-based CD19 CAR-T,IM19,which is promising for further development and clinical investigation.展开更多
The transcription factor ABSCISIC ACID INSENSITIVE5(ABI5)plays a crucial role in abscisic acid(ABA)signaling during seed germination.However,how ABI5 is regulated during this process is poorly understood.Here,we repor...The transcription factor ABSCISIC ACID INSENSITIVE5(ABI5)plays a crucial role in abscisic acid(ABA)signaling during seed germination.However,how ABI5 is regulated during this process is poorly understood.Here,we report that the ubiquitin E3 ligase MIEL1 and its target transcription factor MYB30 modulate ABA responses in Arabidopsis thaliana during seed germination and seedling establishment via the precise regulation of ABI5.MIEL1 interacts with and ubiquitinates ABI5 to facilitate its degradation during germination.The transcription factor MYB30,whose turnover is mediated by MIEL1 during seed germination,also interacts with ABI5 to interfere with its transcriptional activity.MYB30 functions downstream of MIEL1 in the ABA response,and both are epistatic to ABI5 in ABA-mediated inhibition of seed germination and postgerminative growth.ABA treatment induces the degradation of MIEL1 and represses the interaction between MIEL1 and ABI5/MYB30,thus releasing both ABI5 and MYB30.Our results demonstrate that MIEL1 directly mediates the proteasomal degradation of ABI5 and inhibits its activity via the release of its target protein MYB30,thus ensuring precise ABA signaling during seed germination and seedling establishment.展开更多
2 mm low carbon steel plates were successfully welded by the flat friction stir spot welding(FSSW) using double side adjustable tools, by which the keyhole formed in the conventional FSSW was eliminated and a flat sur...2 mm low carbon steel plates were successfully welded by the flat friction stir spot welding(FSSW) using double side adjustable tools, by which the keyhole formed in the conventional FSSW was eliminated and a flat surface on both the top and bottom sides of the welded joints was obtained. In addition, the hook shape usually generated in the conventional FSSW was eliminated by this technique, and the unbonded interface was parallel to the surface of the sheets. Owing to the enlarged bonded interface width by eliminating the keyhole and the intermixed interface by the adjustable probe, the plug fracture occurred under all the welding conditions in the present study. Due to the suppression of the thickness thinning and elimination of the hook shape, the joint performance was improved in the plug fracture mode. The shear tensile performance was considered to strongly depend on the microstructure in the tip area of the unbonded interface and the maximum shear fracture load of 23.0 kN was achieved in this study.展开更多
Dissimilar welding of AZ31/ZK60 magnesium alloys with a thickness of 2 mm was successfully carried out by the double-sided friction stir spot welding with adjustable probes.A dissimilar joint bearing flat surfaces on ...Dissimilar welding of AZ31/ZK60 magnesium alloys with a thickness of 2 mm was successfully carried out by the double-sided friction stir spot welding with adjustable probes.A dissimilar joint bearing flat surfaces on both sides without a keyhole was obtained and the shear failure load of 8.7±0.5 kN was reached.The role of the adjustable probes has been revealed in detail.In the center of the stir zone,the welding interface structure was heterogeneous around which some distinct oxides still remained,leading to a weak interface strength.On the contrary,the welding interface structure around the shoulder/probe interface was homogeneous with no oxides giving rise to a strong interface strength,which is attributed to the severe material flow introduced by the adjustable probes.In addition,the vicinity outside the shoulder/probe interface,where the fracture occurred during the shear tensile tests,was also strengthened owing to the shearing and torsion by the adju stable probes.Therefore,a stable plug failure can be obtained and the joint properties can be improved.展开更多
Design and development of iron porphyrin-based artificial enzymes system have been attracting a lot of attention.Herein,without any toxic reductant and harsh processing,we present a facile one-pot method to fabricate ...Design and development of iron porphyrin-based artificial enzymes system have been attracting a lot of attention.Herein,without any toxic reductant and harsh processing,we present a facile one-pot method to fabricate bifunctional catalytic nanocomposites consisting of graphene and hemin by using vitamin C as a mild reduction reagent.The presence of graphene helps the formation of a high degree of highly active and stable hemin on the graphene surface in a monomeric form through theirπ-πstacking interaction.As a result,such nanocomposites possess a superior adsorption capacity and intrinsic peroxidase-like catalytic activity.Moreover,by the combination of their dye adsorption ability,RGOhemin nanocomposites can serve as a suitable candidate for efficient capture and removal of dyes via a synergistic effect.Our findings may pave the way to apply graphene-supported artificial enzymes in a variety of fields,such as environmental chemistry,bionics,medicine,and biotechnology.展开更多
基金supported in part by the National Natural Science Foundation of China(Nos.62372083,62072074,62076054,62027827,62002047)the Sichuan Science and Technology Innovation Platform and Talent Plan(No.2022JDJQ0039)+2 种基金the Sichuan Science and Technology Support Plan(Nos.2024NSFTD0005,2022YFQ0045,2022YFS0220,2023YFS0020,2023YFS0197,2023YFG0148)the CCF-Baidu Open Fund(No.202312)the Medico-Engineering Cooperation Funds from University of Electronic Science and Technology of China(Nos.ZYGX2021YGLH212,ZYGX2022YGRH012).
文摘Information steganography has received more and more attention from scholars nowadays,especially in the area of image steganography,which uses image content to transmit information and makes the existence of secret information undetectable.To enhance concealment and security,the Steganography without Embedding(SWE)method has proven effective in avoiding image distortion resulting from cover modification.In this paper,a novel encrypted communication scheme for image SWE is proposed.It reconstructs the image into a multi-linked list structure consisting of numerous nodes,where each pixel is transformed into a single node with data and pointer domains.By employing a special addressing algorithm,the optimal linked list corresponding to the secret information can be identified.The receiver can restore the secretmessage fromthe received image using only the list header position information.The scheme is based on the concept of coverless steganography,eliminating the need for any modifications to the cover image.It boasts high concealment and security,along with a complete message restoration rate,making it resistant to steganalysis.Furthermore,this paper proposes linked-list construction schemeswithin theproposedframework,which caneffectively resist a variety of attacks,includingnoise attacks and image compression,demonstrating a certain degree of robustness.To validate the proposed framework,practical tests and comparisons are conducted using multiple datasets.The results affirm the framework’s commendable performance in terms of message reduction rate,hidden writing capacity,and robustness against diverse attacks.
文摘Objective: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. The prognostic factor currently used is not accurate enough to predict the outcomes of patients with DLBCL. The prognostic significance of interim PET/CT in DLBCL remains controversial. The aim of this study is to determine the predictive value of interim 18F-FDG PET/CT after first-line treatment in patients with DLBCL. Methods: Thirty-two patients with DLBCL underwent baseline, interim and post-treatment lSF-FDG PET/CT scans. Imaging results were analyzed for the survival of patients via software SPSS 13.0, retrospectively. Results: Thirty-one of the 32 patients were treated with R-CHOP regimen, and interim 18F-FDG PET/CT of 24 patients was performed after 2 cycles of treatment. After a median follow-up period of 16.7 months, the 2-year progression-free survival (PFS) rates were significantly different between the groups above and below SUVmax CUt-Off value of 2.5 (P=0.039). No significant differences were found in the 2-year PFS rates if SUVm, cut-offvalues were set as 2.0 and 3.0, respectively (P=0.360; P=0.113). Conclusions: Interim PET/CT could predict the prognosis of DLBCL patients with the SUVmax cut-off value of 2.5, but more clinical data should be concluded to confirm this conclusion.
基金sponsored by Scientific Research Foundation for the Returned Overseas Chinese ScholarsMinistry of Human Resources and Social SecurityBeijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(No.XMLX201502)
文摘Objective: High-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT) is the standard of care in the upfront or relapsed/refractory setting in some patients with non-Hodgkin lymphoma (NHL). However, a proportion of patients do not respond to ASCT. lSF-fluorodeoxyglueose (FDG) positron emission tomography (PET)/computed tomography (CT) has been widely used for staging, response evaluation, and prognosis prediction. Here, we investigated the prognostic role of PET/CT in NHL patients before and after ASCT. Methods: A retrospective study was conducted at Peking University Cancer Hospital. All NHL patients who underwent ASCT between March 2010 and July 2016 were identified. Patients who had PET/CT scan before and after ASCT were included. Deauville criteria (5-point scale) were used to interpret PET scans. Univariate and multivariate survival analyses were performed using Cox regression. The predictive value of PET scanning was estimated by comparing the area under the receiver operating characteristic (ROC) curve. Results: In total, 79 patients were enrolled in this study. In univariate analysis, pre- and post-ASCT PET result was identified as prognostic factors for 3-year progression-free survival (PFS) and overall survival (OS). Patients with negative pre-ASCT PET result demonstrated significantly better PFS (84.2% vs. 54.2%) and OS (89.2% vs. 63.6%) than patients with positive pre-ASCT PET result. PFS (91.6% vs. 25.3%) and OS (96.5% vs. 36.8%) were also significantly different between patients with negative and positive post-ASCT PET result. Multivariate analysis also showed a significant association between survival and post-ASCT PET result. ROC analysis revealed that the predictive value of post-ASCT PET result was superior to that of pre-ASCT PET result alone. Combined pre- and post-ASCT PET result is better for predicting outcomes in patients with NHL receiving transplantation. Deauville criteria score 〉3 was identified as the best cutoffvalue for post-ASCT PET. Conclusions: Post-ASCT PET result was more important than pre-ASCT PET result in predicting outcomes for NHL patients who underwent ASCT. The prognostic significance can be improved when combining pre- ASCT PET result with post-ASCT PET result. Deauville criteria can be used for interpreting PET scans in this scenario.
基金sponsored by the Project in the National Science&Technology Pillar Program during the Twelfth Five-year Plan Period(Grant No.2011BAJ07B07)Program for the Philosophy and Social Sciences Research of Higher Learning Institutions of Shanxi(Grant No.115544901002)the National Research Foundation(NRF)Singapore(Grant No.FI 370074011)
文摘The interprovincial trade embodied carbon emissions plays an important role in the national emission reduction target among China's provinces. Furthermore, it will affect the smooth start-up of the national carbon trade market as well as the implementation of targets in 2030 for dealing with the climate change. Based on constructed MRIO model, this paper analyzes the embodied carbon emission trade flows among Beijing, Tianjin, Hebei and surrounding regions such as Shanxi, Shaanxi, and Inner Mongolia. The results indicate that six provinces have formed different patterns of carbon trade balance, where Beijing, Tianjin, and Hebei provinces are in a deficit position, while the other three provinces are in a surplus position.Beijing, Tianjin, and Hebei have transferred part of the carbon emissions to the other three provinces, which shows greater heterogeneity among various provinces and provincial different sectors. On basis of the conclusions, this paper puts forward some suggestions on provincial decomposition, responsibility distribution, and provincial collaborative reduction for national emission reduction targets.
基金supported by the National Natural Science Foundation of China (No. 81600164)
文摘Objective: High-dose chemotherapy(HDC) followed by autologous hematopoietic stem cell transplantation(auto-HSCT) plays an important role in improving outcomes of diffuse large B cell lymphoma(DLBCL) patients.18 F-fluorodeoxyglucose(18 F-FDG) positron emission tomography(PET)/computed tomography(CT) has been widely accepted in response assessment and prediction of prognosis in DLBCL. Here, we report the value of 18 FFDG PET/CT pre-and post-HSCT in predicting outcomes of patients with DLBCL.Methods: DLBCL patients who had PET/CT scan before and after HSCT were included. PET results were interpreted based upon Deauville criteria. The prognostic value of 18 F-FDG PET/CT in auto-HSCT was evaluated.Results: Eighty-four patients were enrolled. In univariate analysis, pre-and post-HSCT PET findings were correlated with 3-year progression-free survival(PFS) [hazard ratio(HR)=4.391, P=0.001; HR=7.607, P<0.001] and overall survival(OS)(HR=4.792, P=0.008; HR=26.138, P<0.001). Patients receiving upfront auto-HSCT after firstline treatment had better outcomes than relapsed/refractory DLBCL patients(3-year PFS, P<0.001; 3-year OS,P<0.001). In the relapsed/refractory patients, pre-and post-HSCT PET findings were also associated with 3-year PFS(P=0.003 vs. P<0.001) and OS(P=0.027 vs. P<0.001). A significant correlation was observed between clinical response to chemotherapy before auto-HSCT and outcomes of patients in the entire cohort(3-year PFS, P<0.001;3-year OS, P<0.001) and in the subgroup of 21 patients with positive pre-HSCT PET(3-year PFS, P=0.084; 3-year OS, P=0.240). A significant association between survival and post-HSCT PET findings was observed in multivariate analysis(HR=5.168, P<0.001).Conclusions: PET results before and after HSCT are useful prognostic factors for DLBCL patients receiving HSCT. Patients who responded to chemotherapy, even those with positive pre-HSCT PET, are appropriate candidates for auto-HSCT.
文摘Objective: Although L-asparaginase(L-ASP) is a standard treatment for lymphoblastic lymphoma(LBL),hypersensitivity reactions by some patients limit its application. Polyethylene glycol-conjugated asparaginase(PEGASP) has a lower immunogenicity and is a standard treatment in all pediatric acute lymphoblastic leukemia(ALL).In this study, we investigated the efficacy and toxicity of PEG-ASP instead of L-ASP as used in the BFM-90regimen(PEG-ASP-BFM-90) for adult LBL.Methods: Between June 2012 and July 2015, we treated 30 adult patients with newly diagnosed LBL, using PEGASP-BFM-90 in a prospective, multicenter and single-arm clinical study at 5 participating institutions in China.Results: All the 30 patients, including 19 males and 11 females with a median age of 30(range: 18–62) years,completed 128 times of the PEG-ASP, with the median of 4(range: 2–6) times. Patients did not receive radiotherapy at this time. The overall response rate was 86.7%(26/30), with 50.0%(15/30) complete response and36.7%(11/30) partial response. The 3-year overall survival was 46.0% [95% confidence interval(95% CI),28.2%–64.8%], and the 3-year progression-free survival was 43.0%(95% CI, 25.7%–62.0%). Major adverse events were myelosuppression, reduced fibrinogen, liver dysfunction and digestive tract toxicities. No allergic reaction and no treatment-related mortality or severe complications were recorded.Conclusions: Our clinical data and observed outcomes indicate that 1 dose of PEG-ASP can replace multiple doses of native L-ASP in BFM-90, with predominantly grade 3–4 neutropenia for adult LBL, and no therapyrelated deaths. The effect is similar to previous reports of PEG-ASP-containing regimens for adult ALL. Major advantages include less serious allergic reactions, 2–3 weeks of action duration, and convenience for patients and physicians.
基金supported by the Beijing Natural Science Foundation (No. 7202026)Capital’s Funds for Health Improvement and Research (No. 2020-2Z-2157)
文摘Objective:Previous studies reported that 4-1BB-based CD19 chimeric antigen receptor(CAR)-T cells were more beneficial for the clinical outcomes than CD28-based CAR-T cells,especially the lower incidence rate of severe adverse events.However,the median progression-free survival(mPFS)of 4-1BB-based product Kymriah was shorter than that of CD28-based Yescarta(2.9 months vs.5.9 months),suggesting that Kymriah was limited in the long-term efficacy.Thus,a safe and durable 4-1BB-based CD19 CAR-T needs to be developed.Methods:We designed a CD19-targeted CAR-T(named as IM19)which consisted of an FMC63 scFv,4-1BB and CD3ζintracellular domain and was manufactured into a memory T-enriched formulation.A phase I/II clinical trial was launched to evaluate the clinical outcomes of IM19 in relapsed or refractory(r/r)B cell non-Hodgkin lymphoma(B-NHL).Dose-escalation investigation(at a dose of 5×10^(5)/kg,1×10^(6)/kg and 3×106/kg)was performed in 22 r/r B-NHL patients.All patients received a single infusion of IM19 after 3-day conditional regimen.Results:At month 3,the overall response rate(ORR)was 59.1%,the complete response rate(CRR)was 50.0%.The mPFS was 6 months and the 1-year overall survival rate was 77.8%.Cytokine release syndrome(CRS)occurred in 13 patients(59.1%),with 54.5%of grade 1−2 CRS.Only one patient(4.5%)experienced grade 3 CRS and grade 3 neurotoxicity.Conclusions:These results demonstrated the safety and durable efficacy of a 4-1BB-based CD19 CAR-T,IM19,which is promising for further development and clinical investigation.
基金supported by the National Natural Science Foundation of China(31872656,32170295,and 31870241)the Natural Science Foundation of Henan(212300410022)the project“the Program for Innovative Research Team(in Science and Technology)in University of Henan Province”(21IRTSTHN019)。
文摘The transcription factor ABSCISIC ACID INSENSITIVE5(ABI5)plays a crucial role in abscisic acid(ABA)signaling during seed germination.However,how ABI5 is regulated during this process is poorly understood.Here,we report that the ubiquitin E3 ligase MIEL1 and its target transcription factor MYB30 modulate ABA responses in Arabidopsis thaliana during seed germination and seedling establishment via the precise regulation of ABI5.MIEL1 interacts with and ubiquitinates ABI5 to facilitate its degradation during germination.The transcription factor MYB30,whose turnover is mediated by MIEL1 during seed germination,also interacts with ABI5 to interfere with its transcriptional activity.MYB30 functions downstream of MIEL1 in the ABA response,and both are epistatic to ABI5 in ABA-mediated inhibition of seed germination and postgerminative growth.ABA treatment induces the degradation of MIEL1 and represses the interaction between MIEL1 and ABI5/MYB30,thus releasing both ABI5 and MYB30.Our results demonstrate that MIEL1 directly mediates the proteasomal degradation of ABI5 and inhibits its activity via the release of its target protein MYB30,thus ensuring precise ABA signaling during seed germination and seedling establishment.
基金financially supported by the New Energy and Industrial Technology Development Organization (NEDO) under the “Innovation Structural Materials Project (Future Pioneering Projects)”。
文摘2 mm low carbon steel plates were successfully welded by the flat friction stir spot welding(FSSW) using double side adjustable tools, by which the keyhole formed in the conventional FSSW was eliminated and a flat surface on both the top and bottom sides of the welded joints was obtained. In addition, the hook shape usually generated in the conventional FSSW was eliminated by this technique, and the unbonded interface was parallel to the surface of the sheets. Owing to the enlarged bonded interface width by eliminating the keyhole and the intermixed interface by the adjustable probe, the plug fracture occurred under all the welding conditions in the present study. Due to the suppression of the thickness thinning and elimination of the hook shape, the joint performance was improved in the plug fracture mode. The shear tensile performance was considered to strongly depend on the microstructure in the tip area of the unbonded interface and the maximum shear fracture load of 23.0 kN was achieved in this study.
基金financially supported by the New Energy and Industrial Technology Development Organization(NEDO)under the“Innovation Structural Materials Project(Future Pioneering Projects)”。
文摘Dissimilar welding of AZ31/ZK60 magnesium alloys with a thickness of 2 mm was successfully carried out by the double-sided friction stir spot welding with adjustable probes.A dissimilar joint bearing flat surfaces on both sides without a keyhole was obtained and the shear failure load of 8.7±0.5 kN was reached.The role of the adjustable probes has been revealed in detail.In the center of the stir zone,the welding interface structure was heterogeneous around which some distinct oxides still remained,leading to a weak interface strength.On the contrary,the welding interface structure around the shoulder/probe interface was homogeneous with no oxides giving rise to a strong interface strength,which is attributed to the severe material flow introduced by the adjustable probes.In addition,the vicinity outside the shoulder/probe interface,where the fracture occurred during the shear tensile tests,was also strengthened owing to the shearing and torsion by the adju stable probes.Therefore,a stable plug failure can be obtained and the joint properties can be improved.
基金supported by the National Nature Science Foundation (Nos.21771150,21401154,U1405226)the Fundamental Research Funds for the Central Universities of China (Nos. 20720170011,20720140528,20720160127)+1 种基金111 Project (No. B16029)Doctoral Fund of the Ministry of Education (No.20130121110018)
文摘Design and development of iron porphyrin-based artificial enzymes system have been attracting a lot of attention.Herein,without any toxic reductant and harsh processing,we present a facile one-pot method to fabricate bifunctional catalytic nanocomposites consisting of graphene and hemin by using vitamin C as a mild reduction reagent.The presence of graphene helps the formation of a high degree of highly active and stable hemin on the graphene surface in a monomeric form through theirπ-πstacking interaction.As a result,such nanocomposites possess a superior adsorption capacity and intrinsic peroxidase-like catalytic activity.Moreover,by the combination of their dye adsorption ability,RGOhemin nanocomposites can serve as a suitable candidate for efficient capture and removal of dyes via a synergistic effect.Our findings may pave the way to apply graphene-supported artificial enzymes in a variety of fields,such as environmental chemistry,bionics,medicine,and biotechnology.