Morphology-Engineering Construction of Anti-Aggregated Co/N-Doped Hollow Carbon from Metal-Organic Frameworks for Efficient Biomass Upgrading.

The controlled pyrolysis of metal/carbon-containing precursors is commonly used for fabricating multifunctional metal/carbon-based catalysts, nevertheless, the inevitable agglomeration of these precursors in pyrolysis is extremely negative for efficient catalysis. This study reports the first example of suppressing the interfacial fusion and agglomeration of metal/carbon-based catalyst in its pyrolysis-involved fabrication process by developing a facile morphology-engineering strategy. Metal-organic framework precursors are chosen as a proof of concept and five Co/N-doped hollow carbons with different morphologies (rhombic dodecahedron, cube, plate, interpenetration twin, and rod) are synthesized via the pyrolysis of their corresponding core-shell ZIF-8@ZIF-67 precursors. It is demonstrated that the interpenetration twin precursor shows the minimum interfacial contact of interparticles due to its partly-concave morphology with abundant facets, which endows it with the best resistibility from interfacial fusion and thus aggregation of interparticles during pyrolysis. Benefiting from its unique anti-aggregated structure with high specific surface area, abundant fully-exposed active sites, and good dispersibility, the resultant 36-facet Co/N-doped hollow carbon exhibit remarkably improved catalytic property for biomass upgrading as compared with its aggregated counterparts. This study highlights the crucial role of engineering morphology to prevent metal/carbon-containing precursors from detrimental agglomeration during pyrolysis, demonstrating a new approach to constructing anti-aggregated metal/carbon-based catalysts.

A sensitive electrochemical aptasensor for zearalenone detection based on target-triggered branched hybridization chain reaction and exonuclease I-assisted recycling.

Traditional methods for detecting antibiotic and mycotoxin residues rely on large-scale instruments, which are expensive and require complex sample pretreatment processes and professional operators. Although aptamer-based electrochemical sensors have the advantages of simplicity, speed, low cost, and high sensitivity, most aptamer-based sensors lack a signal amplification strategy due to their direct use of aptamers as probes, resulting in insufficient sensitivity. To solve the sensitivity problem in the electrochemical detection process, a novel electrochemical sensing strategy was established for ultrasensitive zearalenone (ZEN) detection on the basis of exonuclease I (Exo I) and branched hybridization chain reaction (bHCR) to amplify the signal. The amplification strategy showed excellent analytical performance towards ZEN with a low detection limit at 3.1×10-12 mol/L and a wide linear range from 10-11 to 10-6 mol/L. Importantly, the assay was utilized in the corn powder samples with satisfactory results, holding promising applications in food safety detection and environmental monitoring.

Detection of Pyrophosphate and Alkaline Phosphatase Activity Based on PolyT Single Stranded DNA - Copper Nanoclusters.

The determination of pyrophosphate and alkaline phosphatase activity plays a significant role in medical diagnosis. In this work, a label-free "ON-OFF-ON" fluorescence strategy is developed for the analysis of pyrophosphate and alkaline phosphatase activity. Using PolyT single strand DNA as templates to synthesize fluorescent copper nanoparticles, the coordination effect of pyrophosphoric acid on Cu2+ inhibited the generation of fluorescence. Afterwards, the addition of alkaline phosphatase into hydrolyze pyrophosphoric acid resulted in the release of Cu2+, whereby the fluorescence intensity could be recovered. Thereupon enhanced-sensitivity for alkaline phosphatase was obtained (0.1 mU/L), much better than previously reported methods. Meanwhile, it could be performed directly in homogeneous solution, which was very close to the actual activity level of alkaline phosphatase under physiological conditions. Likewise, satisfactory results were also obtained in specificity assessment, which demonstrated its potential application in clinical diagnosis. Notably, a new, sensitive, low-cost, short-time, and high-sensitivity platform for alkaline phosphatase detection was constructed, and the design of biosensor using DNA-templated Copper nanoclusters (CuNCs) was instructed in this study.

Effect of g-C3N4 on biodiversity and structure of bacterial community in sediment of Xiangjiang River under tetracycline pressure.

Photocatalysts have been widely prepared and used in wastewater treatment. Although the influence of photocatalyst application on survival and activity of organisms has been examined, its impact on composition and diversity of microbial community is not fully understood. In this study, the impact of photocatalyst g-C3N4 (Graphitic carbon nitride) on microbial communities in riverbed sediments polluted by antibiotic tetracycline (TC) was investigated. The sediment samples collected from the Xiangjiang River of China were exposed to different concentrations of TC, g-C3N4 and TC/g-C3N4 and the bacterial community were analyzed by Illumina sequencing. The results showed that the dominant bacterial phyla were Acidobacteriota, Proteobacteria, Actinobacteriota, and Chloroflexi in the study site. When compared to the control treatments, the application of TC, g-C3N4 and TC/g-C3N4 exhibited distinguishable effects on bacterial community structure in sediments. The presence of TC had greater influence on bacterial composition, while g-C3N4 and TC/g-C3N4 had less influence on bacteria. The diversity and richness of microorganisms in sediment increased under g-C3N4 application and reached the highest values when g-C3N4 was 75 mg/kg. The photocatalyst g-C3N4 restored bacterial community diversity affected by TC, reduced the TC residues in aquatic environment, and eliminated the side effects of TC application in sediments. Our study indicated that g-C3N4 was an environmentally friendly photocatalyst with lightly negative effects on microbial community in riverbed sediments, and could be used for effective remediation of TC-contaminated environments.

Improving the safety of CAR-T cell therapy by controlling CRS-related coagulopathy.

The CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy has been widely proved effective on relapsed and refractory (r/r) B cell acute lymphoblastic leukemia (B-ALL). Meanwhile, CAR-T therapy-related toxicities, including cytokine release syndrome (CRS) and neurological toxicities, are drawing researchers' attention. In addition, our research team notices that coagulopathy and even disseminated intravascular coagulation (DIC) are common problems during CAR-T therapy. In our phase 1/2 clinical trial (NCT02965092), 53 r/r B-ALL patients underwent leukapheresis on day - 11 and received lymphodepleting chemotherapy on day - 7 to day - 5. Finally, they received split infusions of anti-CD19 CAR-T cells on day 0 to day 2. Plasma concentrations of tissue factor (TF) and platelet endothelial cell adhesion molecular-1 (PECAM-1) were also measured to identify the mechanism of coagulation disorders. The overall 1-month remission rate of the 53 patients was 88.7%. During the treatment course, 19 patients experienced grade 3-4 CRS, 8 patients developed grade 2-3 neurological toxicities. Beyond that, 30 patients (30/53, 56.6%) suffered from coagulation disorders, and half of them should be diagnosed as DIC. Benefiting from replacement and anticoagulant therapy, 14 patients successfully got out of the conditions of DIC. Remarkably, the severity of coagulopathy was positively correlated with CRS grade. What is more, plasma TF and PECAM-1 levels indicated that vascular endothelial factors played key roles in the process of CRS-related coagulopathy. To conclude, coagulation disorders frequently happen during CAR-T therapy. TF and PECAM-1 are of great importance in the etiology and pathogenesis of coagulation problems. Early and proper interventions targeted at CRS-related coagulopathy contribute a lot to the control of side effects in CAR-T therapy.

Anti-CD19 chimeric antigen receptor-modified T-cell therapy bridging to allogeneic hematopoietic stem cell transplantation for relapsed/refractory B-cell acute lymphoblastic leukemia: An open-label pragmatic clinical trial.

Chimeric antigen receptor-modified T-cell (CAR-T) therapy is effective and safe for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), but its value has been limited in terms of long-term leukemia-free survival. New strategies that can help CAR-T therapy achieve lasting effect are urgently warranted. This non-randomized interventional pragmatic clinical trial had a particular aim. It explored whether consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT) could improve the long-term prognosis of the minimal residual disease-negative complete remission (MRD- CR) patients after CAR-T therapy. In the first stage, 58 r/r B-ALL patients received split doses of CAR-T cells after lymphodepleting chemotherapy, and 51 (87.9%) achieved CR. In the second stage, 21/47 MRD- CR patients without previous allo-HSCT and contraindications or other restrictions, on their own accord, received consolidative allo-HSCT within three months after CAR-T therapy. There was no difference in overall survival (OS) between the MRD- CR patients who received allo-HSCT and those who did not. However, event-free survival (EFS) and relapse-free survival (RFS) were significantly prolonged by allo-HSCT in the subgroups. This was with either high (≥5%) pre-infusion bone marrow MRD assessed by flow cytometry (BM-FCM-MRD) or poor prognostic markers (P < .05). However, no difference was found in EFS and RFS for patients with pre-infusion BM-FCM-MRD <5% and without poor prognostic markers (P > .05). To conclude, CAR-T therapy bridging to allo-HSCT is a safe and effective therapeutic strategy for r/r B-ALL patients, and may prolong their EFS and RFS, especially when they have high pre-infusion BM-FCM-MRD or poor prognostic markers.

Detection of cytokine expression patterns in the peripheral blood of patients with acute leukemia by antibody microarray analysis.

The cytokines of acute leukemia (AL) patients have certain expression patterns, forming a complex network involved in diagnosis, progression, and prognosis. We collected the serum of different AL patients before and after complete remission (CR) for detection of cytokines by using an antibody chip. The expression patterns of cytokines were determined by using bioinformatics computational analysis. The results showed that there were significant differences in the cytokine expression patterns between AL patients and normal controls, as well as between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). In confirmatory test, ELISA revealed the expression of uPAR in AL. Moreover, the bioinformatic analysis showed that the differentially expressed cytokines among the AL groups were involved in different biological behaviors and were closely related with the development of the disease. It was concluded that the cytokine expression pattern of AL patients is significantly different from that of healthy volunteers. Also, differences of cytokine expression patterns exist between AML and ALL, and between before and after CR in the same subtype of AL, which holds important clinical significance for revealing disease progression.

Osteolytic lesions as a presenting sign of acute myeloid leukemia: a case report.

Osteolytic lesions are infrequently observed in adult patients with acute myeloid leukemia (AML). This report details the case of a 66-year-old male patient who presented with myeloid sarcoma (MS), osteolytic lesion and pancytopenia. Effective treatments were delayed due to diagnostic challenges and the rapid progression of the disease. It is essential to consider AML in the differential diagnosis when faced with a patient presenting osteolytic lesions and pancytopenia.

Analysis of hematogones in bone marrow from acute myeloid leukaemia cases posttherapy.

BACKGROUND: Increased bone marrow (BM) hematogones (HGs) are often observed in patients with marrow regenerating status. Many studies have focused on the role of HGs in acute lymphoblastic leukaemia (ALL), but very little has been done to understand their effects on acute myeloid leukaemia (AML). MATERIALS AND METHODS: Through immunophenotyping, HGs were quantified in 471 BM samples from 292 postchemotherapy AML cases. These samples were analysed to determine whether there is any relationship between HGs percentages and French-American-British (FAB) subtypes or risk stratification of AML. RESULTS: HGs were identified in 57.75% of 471 patient samples (271) with a mean percentage of 3.87 ± 0.25%. No significant differences were found amongst different FAB subtypes of AML (P > 0.05). However, significant differences (P < 0.05) in HG numbers were noted between AML patients experiencing haematological complete remission (HCR) and those who have relapsed. HGs were identified in 59.9% of samples under HCR with a mean per cent of 3.98 ± 0.31%, and 36.7% of individuals who have relapsed have detectable HGs with a mean per cent of 1.75 ± 0.47. In addition, HGs in patients groups with low risk or intermediate risk were elevated when compared with high-risk groups (P < 0.05), whilst no significant difference was found between low-risk patients and intermediate-risk patients (P > 0.05). Patients with >0.1% of HGs had a significantly better median leukaemia-free survival (LFS) and overall survival (OS) than those with <0.1% of HGs (P < 0.01). CONCLUSIONS: Therefore, our data indicate that HGs in bone marrow may be used as a favourable prognostic factor that predict for a better outcome of AML patients.

Analysis of seizure risk factors after allogeneic hematopoietic stem cell transplantation: a 8 case report and literature review.

The clinical characteristics of patients with seizures after allogeneic hematopoietic stem cell transplantation (allo-HSCT) were analyzed. A total of 8 cases of seizures after allo-HSCT were investigated. Clinical data of these cases were studied retrospectively. Of 159 cases subjected to allo-HSCT, seizure occurred in 8 cases during 29-760 days after transplantation, median survival time was 46 days, and there were 6 cases of tonic-clonic seizure. The incidence of seizure after matched unrelated HSCT was higher than that after related HSCT (P=0.017). Of 7 cases treated with cyclosporine A (CsA), 4 cases obtained high blood levels of CsA. In addition, hyponatremia was diagnosed in 5 cases. Abnormal electroencephalogram and brain MRI findings were found in some cases. During 20 days after seizure, 2 cases died due to infection and graft-versus-host disease (GVHD), respectively. It was suggested that multiple factors are associated with seizures after allo-HSCT. Rapid identification and correction of the causative factors are very important to prevent permanent central nervous system damage and reduce the mortality.

Case report: nanopore targeted sequencing in the diagnosis of invasive pulmonary Aspergillus infection in a patient with acute promyelocytic leukemia.

Invasive pulmonary aspergillosis (IPA) is an infectious disease with a high mortality rate due to diagnostic difficulties associated with the lack of a typical clinical presentation and the inadequacy of the available laboratory testing methods. Nanopore targeted sequencing (NTS) is an alternative method of broad-based pathogen discovery, associated with rapid turnaround and high accuracy. This case report presents a patient with IPA and acute promyelocytic leukemia, diagnosed using the NTS method, which detected Aspergillus flavus in the patient's blood and pleural fluid. The patient was treated effectively with antifungal therapy. Early diagnosis of IPA improved long-term patient prognosis and quality of life.

A fluorescent assay for sensitive detection of kanamycin by split aptamers and DNA-based copper/silver nanoclusters.

Kanamycin was a group of essential antibiotics generally served in treating infections of animals which leached into the environment residual in food, causing health concerns. Thus, selective and sensitive monitoring of kanamycin was significant for food safety. In this work, split aptamers were used as templates to prepare fluorescent Cu/Ag NCs for detection of kanamycin. According to the impressive affinity of the aptamer to kanamycin, two different detection modes were designed using kanamycin aptamer as a recognition molecule, in which one was to combine split aptamer Apt-1 with Apt-2 to form an entangled DNA as a Cu/Ag NCs template, the other was to associate the normal aptamer after encirclement to form Cu/Ag NCs templates. After the addition of kanamycin, the fluorescence signals of the Cu/Ag NCs synthesized in the two modes were both enhanced, but the approach with split aptamer exhibited a superior observable sensitivity than that of the normal type. The detection range showed a well linear relationship between 80 nM and 10 µM when the emission wavelength was 560 nm, and the detection limit was 13.3 nM. In addition, when streptomycin, oxytetracycline, chloramphenicol and chlortetracycline were involved in the selective interference experiment under the same conditions, the fluorescence intensity of the system performed no significant changes. The results demonstrated that this method possessed favorable specificity and selectivity for the assay of kanamycin, proficiently achieving efficient, rapid and sensitive evaluation of kanamycin in the milk samples.

A novel colorimetric assay for sensitive detection of kanamycin based on the aptamer-regulated peroxidase-mimicking activity of Co3O4 nanoparticles.

Kanamycin is used widely in livestock farming due to its antimicrobial properties and low cost, but has led to antibiotic residues in food, which can damage human health. Therefore, there is an urgent need for convenient technology that can be used to detect kanamycin rapidly. We found that Co3O4 nanoparticles (NPs) possessed peroxidase-like activity that catalyzed the oxidation of 3,3',5,5'-tetramethylbenzidine to change color. Interestingly, a target-specific aptamer could regulate the catalytic activity of Co3O4 NPs and inhibit this effect through aptamer-target binding. On the basis of a colorimetric assay combined with an aptamer-regulatory mechanism, the linear range for quantitative detection of kanamycin was 0.1-30 µM, the minimum limit of detection was 44.2 nM, and the total time needed for detection was 55 min. Moreover, this "aptasensor" displayed excellent selectivity and could be applied to detect KAN in milk samples. Our sensor might have promising applications for kanamycin detection in animal husbandry and agricultural products.

Characterization and application of Fe-modified biochar alleviating Cr(VI) stress in pak choi seedling cultivated in Cr-polluted hydroponics.

Chromium (Cr) is one of the common environmental pollutants, which causes severe health hazards on human health and environmental security. In this study, we characterized two biochars, a raw biochar (RBC) and a Fe-modified biochar (MBC) made from poplar wood chips and determined the effect of the two biochars on remediation of hexavalent chromium (Cr(VI)) in hydroponic system by monitoring Pak choi growth. Results showed the surface area, pore number and pore volume were significantly higher in MBC than in PBC, but the pore size was larger in PBC than in MBC. When compared to the control, low concentrations of Cr(VI) (≤2 mg L-1) promoted the growth and biomass production of Pak choi by 10-78%. In contrast, the high concentrations of Cr(VI) (≥4 mg L-1) showed a significantly reduction of the growth and biomass production of Pak choi by 10-28%. Fe-modified biochar (MBC) had a more significant impact than RBC on the remediation of Cr in the Cr(VI) pollution and improved growth and biomass production of Pak choi to a greater extent. Our study indicated that MBC has a better effect on degrading Cr(VI) pollution. The findings provide scientific basis and reference for the remediation of heavy metals in aquatic ecosystems by using biochar.

Novel ZnFe2O4/BC/ZnO photocatalyst for high-efficiency degradation of tetracycline under visible light irradiation.

Developing broad-spectrum light reactions, effective charge separation, and easily recoverable photocatalysts were considered cost-effective pollution remediation methods. The ZnFe2O4/BC/ZnO composite was prepared to achieve these objectives, where biochar (BC) was used as a conductive channel and ZnFe2O4 as a magnetic substance. Among them, the 0.6-ZBO composite performed the best, with photocatalytic removal of tetracycline (TC) reaching 85.6%. The photocatalytic degradation rated constant of 0.6-ZBO composite was 23.36 × 10-3 min-1, which was 7.6, 4.1, and 2.5 times higher than that of ZnFe2O4/BC, ZnO, and ZnFe2O4/ZnO samples, respectively. According to several characterization data, it was demonstrated that successful Z-scheme heterojunctions were constructed between ZnFe2O4 and ZnO. The 0.6-ZBO complex increased the range of light absorption and strengthened the separation of electron-hole pairs, thus improving the redox ability of the complex. In the different water matrices, the stability of 0.6-ZBO was excellent and its ability to remove TC decreased slightly to about 11% after 5 cycles. This work provided a valuable approach to design a novel and efficient system for degrading organic pollutants in wastewater using magnetic biochar.

A Novel Risk Predictive Scoring Model for Predicting Subsequent Infection After Carbapenem-Resistant Gram-Negative Bacteria Colonization in Hematological Malignancy Patients.

Background: This study investigated the high-risk factors associated with the increased vulnerability for subsequent clinical CR-GNB infection in carbapenem-resistant Gram-negative bacteria (CR-GNB)-colonized hematological malignancy (HM) patients and built a statistical model to predict subsequent infection. Method: All adult HM patients with positive rectoanal swabs culture for CR-GNB between January 2018 and June 2020 were prospectively followed to assess for any subsequent CR-GNB infections and to investigate the risk factors and clinical features of subsequent infection. Results: A total of 392 HM patients were enrolled. Of them, 46.7% developed a subsequent clinical CR-GNB infection, with 42 (10.7%) cases of confirmed infection and 141 (36%) cases of clinically diagnosed infection. Klebsiella pneumoniae was the dominant species. The overall mortality rate of patients colonized and infected with CR-GNB was 8.6% and 43.7%. A multivariate analysis showed that remission induction chemotherapy and the duration of agranulocytosis, mucositis, and hypoalbuminemia were significant predictors of subsequent infection after CR-GNB colonization. According to our novel risk-predictive scoring model, the high-risk group were >3 times more likely to develop a subsequent infection in comparison with the low-risk group. Conclusion: Our risk-predictive scoring model can early and accurately predict a subsequent CR-GNB infection in HM patients with CR-GNB colonization. The early administration of CR-GNB-targeted empirical therapy in the high-risk group is strongly recommended to decrease their mortality.

The effects of g-C3N4/biochar and g-C3N4 on bacterial community in riverbed sediment.

Biochar had been widely used to improve the activity of photocatalysts, the biochar-based photocatalysts had more potential for environmental pollution remediation, but their effect on the sediment remained unknown. To understand these, the typical photocatalyst g-C3N4 was modified by biochar to develop g-C3N4/biochar with enhanced photocatalytic ability. Riverbed sediment was exposed to g-C3N4 and g-C3N4/biochar respectively for 30 days, and Illumina sequencing was utilized to examine the changes in the bacterial community in the sediment. The results showed that in riverbed sediment, g-C3N4 exposure had a concentration-dependent effect on the diversity of bacteria, while g-C3N4/biochar exposure had a slight influence on the bacterial diversity and the diversity almost maintained stable with different g-C3N4/biochar concentration. The application of g-C3N4 exhibited an inhibition influence on the growth of Acidobacteria, Gemmatimonadetes, and Rokubacteria in sediment, whose relative abundance increased when g-C3N4 was 25 mg/kg, and then decreased when g-C3N4 beyond this concentration. The presence of g-C3N4/biochar increased the relative abundance of Cyanobacteria in sediment and showed no obvious impact on other dominant phyla. Both g-C3N4 and g-C3N4/biochar could alter the levels of TP, NN, and AN in the sediment, but the magnitude of the changes of these physicochemical factors caused by g-C3N4/biochar was much smaller than those caused by g-C3N4. In addition, the complexity of the bacterial community network was reduced in a high concentration of g-C3N4, while it remained stable with different concentrations of g-C3N4/biochar treatments. Totally, this study demonstrated that, compared to g-C3N4, g-C3N4/biochar was able to maintain the relative stability of the bacterial community in riverbed sediment and mitigate the negative effects of photocatalysts to some extent, making biochar an ecological remediation agent with great potential for application.

Effects of g-C3N4 on bacterial community and tetracycline resistance genes in two typical sediments in tetracycline pollution remediation.

Photocatalysis, as a novel technique, has been widely used for antibiotic pollution remediation in wastewater. In the processes of degradation and removal of antibiotics, the impact of photocatalysts on microenvironment is very important but remains poorly understood. In the present study, the effect of typical photocatalyst g-C3N4 (Graphitic carbon nitride) on microbial community was investigated in two sediment types (riverbed sediment and pig-farm sediment) polluted by tetracycline (TC) in central southern China. The riverbed sediment and pig farm sediment samples were respectively exposed to g-C3N4 (25, 75, 125 mg⋅kg-1) and TC (60, 120, 180 mg⋅L-1) treatments alone or combination for 30 days, respectively. The bacterial community and antibiotic resistance genes (ARGs) of the treated sediments were analyzed by Illumina sequencing and metagenomic sequencing. Studies had shown that: TC, g-C3N4, and TC/g-C3N4 have significant effects on the changes of microbial communities and components in riverbed sediment, but they do not exist in pig farm sediment. The most alterations of microbial taxa were Acidobacteriota, Actinobacteriota, and Desulfobacterota in riverbed sediment, and Elusimicrobiota in the pig farm sediment under various treatments. Through network analysis, it was found that the distribution of microorganisms in the pig farm sediment is more complex and more stable. The addition of g-C3N4 reduced the absolute abundance of ARGs in the two examined sediments, but not significantly changed their relative abundance of ARGs. The g-C3N4 application was beneficial to the removal of TC residues and to the prevention of the generation and transmission of ARGs in sediments. Our results suggested that g-C3N4 was a suitable photocatalyst with excellent application prospect for the removal of TC residues and the control of ARGs in environment.

Efficacy and safety of chimeric antigen receptor T cell immunotherapy in B-cell non-Hodgkin lymphoma: a systematic review and meta-analysis.

Aim: The aim was to evaluate the efficacy and safety of chimeric antigen receptor T (CAR-T) cell in B-cell non-Hodgkin lymphoma (B-NHL). Materials & methods: A meta-analysis was conducted using eligible clinical trials, which were obtained from electronic medical literature databases. Results: A total of 24 clinical trials with 590 patients were included. The best overall response rate was 66% and complete remission rate was 46%. The incidence rates of cytokine-release syndrome and neurotoxicity (grade ≥ 3) were 9 and 5%, respectively. The various clinical factors were analyzed. Autogenic CAR-T cell may lead to improved efficacy than allogeneic CAR-T cell. CD20 CAR-T cell may show increased efficacy than CD19 CAR-T cell. Conclusion: CAR-T immunotherapy has remarkable efficacy and low toxicity in relapsed/refractory B-NHL.