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The electrochemical dimerization of acrylonitrile (AN) to adiponitrile (ADN) is an essential process for nylon-66 production, but this process still faces many challenges such as low energy conversion efficiency and poor selectivity. Herein, various ionic liquids (ILs) were used as electrolyte additives to evaluate their effects on the electrochemical dimerization of AN. The addition of IL significantly enhanced the performance of the electrolytic reaction and inhibited the hydrogen evolution reaction (HER). The electrolyte containing Tetrabutylphosphonium bromide (TBPB) showed the highest faraday efficiency of adiponitrile (FEADN) of 84.5% and excellent stability at an optimal current density of 200 mA cm–2. Molecular dynamics (MD) simulations revealed that TBPB was uniformly dispersed in the electrolyte and formed a “long brush” hydrophobic layer with appropriate wettability on the electrodes. Moreover, it was observed that ILs with a more symmetrical cationic structure exhibited a better hydrophobic layer effect, favoring the dimerization of AN to ADN.

The separation of CO2from the industrial post-combustion flue gas is of great importance to reduce the increasingly serious greenhouse effect, yet highly challenging due to the extremely high stability, low cost, and high separation performance requirements for adsorbents under the practical operating conditions. Herein, we report a robust squarate-cobalt metal–organic framework (MOF), FJUT-3, featuring an ultra-small 1D square channel decorated with −OH groups, for CO2/N2separation. Remarkably, FJUT-3 not only has excellent stability under harsh chemical conditions but also presents low-cost property for scale-up synthesis. Moreover, FJUT-3 shows excellent CO2separation performance under various humid and temperature conditions confirmed by the transient breakthrough experiments, thus enabling FJUT-3 with adequate potentials for industrial CO2capture and removal. The distinct CO2adsorption mechanism is well elucidated by theoretical calculations, in which the hierarchical C···OCO2, C–O···CCO2, and O–H···OCO2interactions play a vital synergistic role in the selective CO2adsorption process.

The increasing CO2emission, as the chief culprit causing numerous environmental problems, could be addressed by the electrochemical CO2reduction (CO2R) to the added-value carbon-based chemicals. Ionic liquids (ILs) as electrolytes and co-catalysts have been widely studied to promote CO2R owing to their unique advantages. Among the potential products of CO2R, those only containing one carbon atom, named C1 products, including CO, CH3OH, CH4, and syngas, are easier to achieve than others. In this study, we first summarized the research status on CO2R to these C1 products, and then, the state-of-the-art experimental results were used to evaluate the economic potential and environmental impact. Considering the rapid development in CO2R, future scenarios with better CO2R performances were reasonably assumed to predict the future business for each product. Among the studied C1 products, the research focuses on CO, where satisfactory results have been achieved. The evaluation shows that producing CO viaCO2R is the only profitable route at present. CH3OH and syngas of H2/CO (1 : 1) as the targeted products can become profitable in the foreseen future. In addition, the life cycle assessment (LCA) was used to evaluate the environmental impact, showing that CO2R to CH4is the most environmentally friendly pathway, followed by the syngas of H2/CO (2 : 1) and CO, and the further improvement of the CO2R performance can make all the studied C1 products more environmentally friendly. Overall, CO is the most promising product from both economic and environmental impact aspects.Keywords: Electrochemical-CO2-reduction; Ionic-liquids; C1-product; Economic-evaluation; Environmental-impact.

Carboxymethyl lignocellulose/montmorillonite composite (CNC/MMT) was prepared by intercalation-polymerization with carboxymethyl lignocellulose (CNC) and montmorillonite (MMT). When the mass ratio of carboxymethyl lignocellulose and montmorillonite of 0.5:1, preparation time of 6 h, and preparation temperature of 60°C, the declining values after treatment of chemical oxygen demand (COD) and ammonia nitrogen (NH3–N) in monosodium glutamate wastewater (MSGW) by CNC/MMT are 8,786 and 3,700 mg/L, respectively. The carboxymethyl lignocellulose/montmorillonite was characterized by scanning electron microscopy, transmission electron microscopy, Brunauer–Emmett– Teller, Fourier-transform infrared spectroscopy, X-ray diffraction, and thermogravimetric analysis. The results showed that the –COO– in carboxymethyl lignocellulose and Si–OH in montmorillonite form CNC/MMT with rough surface through complexation and coordination, and the crystal structure of montmorillonite is destroyed, forming intercalation-exfoliation carboxymethyl lignocellulose/mont-morillonite. The effects of carboxymethyl lignocellulose/montmorillonite on the removal capacity of COD and NH3–N in MSGW were investigated by changing the experimental conditions. When the mass of carboxymethyl lignocellulose/montmorillonite of 0.1 g, the contact temperature of 60°C, and contact time of 6 h, the declining values of COD and NH3–N are 8,979 and 3,884 mg/L, respectively.

Alfalfa (Medicago sativaL.) is the most widely cultivated perennial leguminous forage crop woldwide. MicroRNA156 (miR156) precursor genes from dicotyledonous species are reportedly useful for improving alfalfa plant architecture and abiotic stress resistance. However, there has been no report on whether a miR156 precursor gene from a monocotyledonous species functions in alfalfa. We introduced two tandem precursor genes of miR156, rice Osa-MIR156band Osa-MIR156c(Osa-MIR156bc), into alfalfa. The expression of miR156 in the transgenic (TG) alfalfa was significantly elevated. Compared to wild-type plants, the TG plants overexpressing miR156 had more branches and leaves and showed improved salt and drought tolerance. Overexpression of miR156 slightly reduced plant height, but the biomass yield of TG plants grown in flowerpots was still increased. Forage quality of TG plants was markedly improved by reduction of acid detergent lignin (ADL) content and increase in crude protein content. The expression of the putative miR156 target genes MsSPL6, MsSPL12, and MsSPL13in TG plants was repressed by miR156 overexpression, and that of all tested MsSPLs would be sharply increased under drought or salt stress. RNA sequencing revealed that overexpression of miR156 affected the expression of genes associated with abiotic stress resistance and plant development in multiple pathways. This first report of overexpression of monocot miR156 precursors in alfalfa sheds light on the function of miRNA156 precursors from the monocot species rice that could be used for genetic improvement of the dicot forage crop alfalfa.

Conducting fibers with improved properties and functionalities are needed for diverse applications. Here we report the fabrication of core/shell conductive Dacron fibers by dip-coating method through originating from multi-walled carbon nanotubes (MWCNTs) coated on polyester fibers. The annealing process was conducted to enhance interaction between the conductive shell and polyester core as well as within the MWCNTs network. The properties of two kinds of MWCNTs dispersions and the electrical properties of conductive fibers were studied, respectively. The results show that both MWCNTs-polyurethane resin (MWCNTs-WPU) dispersion and MWCNTs-acrylic resin (MWCNTs-PAA) dispersion present a typical characteristic of pseudo-plastic fluid and an excellent wetting ability to polyester fibers. The ultimate tensile stress and elongation at break for the MWCNTs-PAA coated fiber are 261 MPa and 25.43%. The ultimate tensile stress and the elongation at break are both increasing with the increasing of MWCNTs contents, due to the strong interface bonding ability between the conductive shell and polyester core and strengthen the MWCNTs network. The electrical resistance of the obtained fibers can be controlled in the range from 732 to 30 Ω/cm by changing MWCNTs content, dipping times and annealing temperature. It was found that it is able to light a LED. All results suggest that the conductive fibers embody a good synergy effect of carbon nanotubes and polymers. Therefore, the fabricated conductive fibers have a widely prospect for being applied in the field of flexible electronics.

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The CO2solubilities (including CO2Henry's constant) in physical- and chemical-based ILs/DESs and the COSMO-RS models describing these properties were comprehensively collected and summarized. The summarized results indicate that chemical-based ILs/DESs are superior to physical-based ILs/DESs for CO2capture, especially those ILs have functionalized cation and anion, and superbase DESs; some of the superbase DESs have higher CO2solubilities than those of ILs; the best physical- and chemical-based ILs, as well as physical- and chemical-based DESs are [BMIM][BF4] (4.20 mol kg−1), [DETAH][Im] (11.91 mol kg−1), [L-Arg]-Gly 1:6 (4.92 mol kg−1) and TBD-EG 1:4 (12.90 mol kg−1), respectively. Besides the original COSMO-RS mainly providing qualitative predictions, six corrected COSMO-RS models have been proposed to improve the prediction performance based on the experimental data, but only one model is with universal parameters. The newly determined experimental results were further used to verify the perditions of original and corrected COSMO-RS models. The comparison indicates that the original COSMO-RS qualitatively predicts CO2solubility for some but not all ILs/DESs, while the quantitative prediction is incapable at all. The original COSMO-RS is capable to predict CO2Henry's constant qualitatively for both physical-based ILs and DESs, and quantitative prediction is only available for DESs. For the corrected COSMO-RS models, only the model with universal parameters provides quantitative predictions for CO2solubility in physical-based DESs, while other corrected models always show large deviations (> 83%) compared with the experimental CO2Henry's constants.

Methanol is a future energy carrier because of its high volume-specific energy density and a significant intermediate for many bulk chemicals. Electrochemical reduction is a promising method to fabricate methanol (CH3OH) from carbon dioxide (CO2) where electrocatalyst, reactor configuration, and electrode play an essential role. In this review, seven types of electrocatalysts, that is, metal alloys, metal oxides, metal chalcogenides and carbides, metal–organic complexes, metal–free pyridine and metal–organic framework–based electrocatalysts, as well as the effect of reactor configuration and electrode were comprehensively summarized. Finally, challenges and perspectives on developing electrocatalysts were highlighted.

Colorectal cancer (CRC) is a common cancer type and a threat to human health. Tumor budding (TB) is the presence of a single cancer cell or clusters of up to five cancer cells prior to the invasive front of an aggressive carcinoma and is an independent prognosis factor for CRC. The molecular mechanism of TB is still unclear, and drugs that inhibit this process are still in the blank stage. This study found that TBs exhibit characteristics of partial EMT with a decreased expression of E-cadherin and no substantial differences in the expression of N-cadherin and vimentin. We also observed the interaction of integrin with extracellular matrix components, laminin-5γ2 (LN-5γ2), play essential roles in the TB of CRC. We then verified that the interaction between LN-5γ2 and integrin β1 promotes the TB of CRC via the activation of FAK and Yes-associated proteins (YAP). A natural drug monomer, cucurbitacin B, was screened using virtual screening methods for the interaction interface of proteins. We found that this monomer could block the interaction interface between LN-5γ2 and integrin β1 and substantially inhibit the TB of CRC cells via inactivation of YAP. This study provides new insights into the mechanism of TB mechanism and the development of drugs targeting the TB of CRC.

Background: With the approval of gefitinib, erlotinib, afatinib, and osimertinib for clinical use, targeting Epidermal Growth Factor Receptor (EGFR) has been intensively pursued. Similar to most therapies, challenges related to the treatment resistance against these drugs have emerged over time, so new EGFR Tyrosine Kinase Inhibitors (TKIs) need to be developed. This study aimed to investigate the potential use of a series of thiophene-bearing quinazoline derivatives as EGFR inhibitors. We designed and synthesized nine quinazolin derivatives, among which five compounds (5e, 5f, 5g, 5h, and 5i) were reported for the first time. Methods: Two cancer cell lines, A431 (overexpressing EGFR) and A549 (EGFR wild-type and Kras mutation), were treated by these compounds and subjected to MTT assay. The A431 cells were selected for further treatment (5e) and Western blot analysis. Results: Although the compounds exerted no obvious effects on the proliferation of A549 cells, seven out of the nine compounds significantly inhibited the growth of A431 cells. In particular, the IC50 values of 5e and erlotinib were nearly equal. Western blot results showed that 5e significantly inhibited EGFR autophosphorylation in A431 cells. Structure-activity relationships indicated that quinazolines bearing 6,7-side chains were more potent than those unsubstituted at the 6,7-positions. Moreover, electron-withdrawing hydrophobic groups on the 5-position of the thiophene were preferred, such as chlorine or bromine atom. Conclusion: Nine 4-aminoquinazolin derivatives were designed, synthesized, and evaluated against A431 and A549 cell lines. Seven compounds significantly inhibited the growth of A431 cells. In particular, 5e possessed similar antitumor potency to that of erlotinib.

Background:The level of MRD before and after transplantation is related to inferior transplant outcomes, and post-hematopoietic stem cell transplantation measurable residual disease (post-HSCT MRD) has higher prognostic value in determining risk than pre-HSCT MRD. However, no work has been devoted to the risk factors for positive post-HSCT MRD in patients with ALL. This study evaluated the risk factors for post-HSCT MRD positivity in patients with acute lymphoblastic leukemia (ALL) who underwent allogeneic HSCT (allo-HSCT).

This study was aimed to investigate the effects of yeast polysaccharides (YPS) on growth performance, intestinal health, and aflatoxin metabolism in livers of broilers fed diets naturally contaminated with mixed mycotoxins (MYCO). A total of 480 one-day-old Arbor Acre male broilers were randomly allocated into a 2 × 3 factorial arrangement of treatments (8 replicates with 10 birds per replicate) for 6 wk to assess the effects of 3 levels of YPS (0, 1, or 2 g/kg) on the broilers fed diets contaminated with or without MYCO (95 μg/kg aflatoxin B1, 1.5 mg/kg deoxynivalenol, and 490 μg/kg zearalenone). Results showed that mycotoxins contaminated diets led to significant increments in serum malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels, mRNA expressions of TLR4and 4EBP1associated with oxidative stress, mRNA expressions of CYP1A1, CYP1A2, CYP2A6, and CYP3A4associated with hepatic phase Ⅰ metabolizing enzymes, mRNA expressions of p53associated with hepatic mitochondrial apoptosis, and AFB1residues in the liver (P< 0.05); meanwhile dietary MYCO decreased the jejunal villus height (VH), villus height/crypt depth (VH/CD), the activity of serum total antioxidant capacity (T-AOC), mRNA expressions of jejunal HIF-1α, HMOX, and XDHassociated with oxidative stress, mRNA expressions of jejunal CLDN1, ZO1, and ZO2, and mRNA expression of GSTassociated with hepatic phase Ⅱ metabolizing enzymes of broilers (P< 0.05). Notably, the adverse effects induced by MYCO on broilers were mitigated by supplementation with YPS. Dietary YPS supplementation reduced the concentrations of serum MDA and 8-OHdG, jejunal CD, mRNA expression of jejunal TLR2, and 4EBP1, hepatic CYP1A2, and p53, and the AFB1residues in the liver (P< 0.05), and elevated the serum T-AOC and SOD, jejunal VH, and VH/CD, and mRNA expression of jejunal XDH, hepatic GSTof broilers (P< 0.05). There were significant interactions between MYCO and YPS levels on the growth performance (BW, ADFI, ADG, and F/G) at d 1 to 21, d 22 to 42, and d 1 to 42, serum GSH-Px activity, and mRNA expression of jejunal CLDN2and hepatic rasof broilers (P< 0.05). In contrast with MYCO group, the addition of YPS increased BW, ADFI, and ADG, the serum GSH-Px activity (14.31%–46.92%), mRNA levels of jejunal CLDN2(94.39%–103.02%), decreased F/G, and mRNA levels of hepatic ras(57.83%–63.62%) of broilers (P< 0.05). In conclusion, dietary supplements with YPS protected broilers from mixed mycotoxins toxicities meanwhile keeping normal performance of broilers, presumably via reducing intestinal oxidative stress, protecting intestinal structural integrity, and improving hepatic metabolic enzymes to minimize the AFB1residue in the liver and enhance the performance of broilers.

Hepatocellular carcinoma (HCC) ranks as one of the most common and lethal malignancies worldwide. A better understanding of the mechanism responsible for HCC metastasis will be helpful for the treatment of HCC patients. Thymidine phosphorylase (TP), a key enzyme that catalyzes the conversion of thymidine to thymine and deoxyribose-1-phosphate, was demonstrated to promote the invasion and metastasis of HCC in our study. Clinical retrospective analysis revealed that metastatic HCC tumor tissues have higher TP expression, and TP expression was significantly correlated with matrix metalloproteinase (MMP) 2 and 9 expression. Survival analysis revealed that TP expression was negatively correlated with the prognosis of HCC patients. Moreover, in vitro cell experiments confirmed that TP could promote the migration and invasion of HCC cells. In addition, MMP2 and MMP9 were activated by TP overexpression. Overall, this study suggests that TP promotes metastasis and may serve as a marker of poor prognosis in HCC. Thus, TP is a potential target for the treatment of HCC.

Hepatocellular carcinoma (HCC) ranks as one of the most common and lethal malignancies worldwide. A better understanding of the mechanism responsible for HCC metastasis will be helpful for the treatment of HCC patients. Thymidine phosphorylase (TP), a key enzyme that catalyzes the conversion of thymidine to thymine and deoxyribose-1-phosphate, was demonstrated to promote the invasion and metastasis of HCC in our study. Clinical retrospective analysis revealed that metastatic HCC tumor tissues have higher TP expression, and TP expression was significantly correlated with matrix metalloproteinase (MMP) 2 and 9 expression. Survival analysis revealed that TP expression was negatively correlated with the prognosis of HCC patients. Moreover, in vitrocell experiments confirmed that TP could promote the migration and invasion of HCC cells. In addition, MMP2 and MMP9 were activated by TP overexpression. Overall, this study suggests that TP promotes metastasis and may serve as a marker of poor prognosis in HCC. Thus, TP is a potential target for the treatment of HCC.

Hydrogen is believed to be one of the essential clean secondary energy sources in the energy structure revolution of both industry and daily life. Driven by renewable electricity such as solar and wind power, water electrolysis for hydrogen production is deemed as one of the main processes of green hydrogen production in the future by both academia and industry. Transition metal chalcogenides (TMCs) are promising candidates to replace noble metals as earth-abundant electrocatalysts for water splitting. However, it remains challenging to further improve the electrocatalytic activity and long-term stability of TMCs, especially in a practical water electrolyzer. This Review summarizes the recent advances and the strategies of optimizing the electrocatalytic activities of TMCs toward water splitting as well as the latest investigations on the surface reconstructions of TMCs during water electrolysis. The performances of TMCs in practical electrocatalytic water splitting cells are particularly discussed. Finally, a concluding remark and perspective is provided, and we hope to inspire future works in this area, narrowing the gap between material design and practical application.

In this paper, we evaluated the effect of seven stabilizers with different shapes (including cylinder, cubic and ball shape) on zircon U–Pb dating analysis by laser ablation inductively coupled plasma quadrupole mass spectrometry (LA-ICP-QMS) in detail. In the case of stabilizer volume examined, the analytical efficiency of cylinder stabilizers (21.2, 25.1, 35.3 and 125 mL) were investigated in terms of signal stabilization, signal rising/washout time and U–Pb dating accuracy. By using zircon 91500 as reference material for external calibration, the 206Pb/238U age of zircon Plešovice was determined by a nanosecond LA-ICP-QMS, where the stabilizer was placed directly after the ablation cell and sample aerosols carried by helium passed through the stabilizer and subsequently mixed with make-up gas (argon) before ICP. It was found that transient signal oscillations were invisible and signal intensities were comparable using all the stabilizers, while signal rising time was 2.0-fold and washout time was 27.6-fold for stabilizer with volume of 125 mL to that of 21.2 mL. The obtained average 206Pb/238U age of zircon Plešovice was 335.53 ± 1.02, 361.73 ± 5.04, 340.10 ± 1.98 and 341.21 ± 5.17 Ma (2σ, n≥ 5), respectively, giving average relative deviations of a single point of age (1σ) less than 2.0%. Among the corresponding 206Pb/238U ratios, it was also found that the value (0.05343 ± 0.87‰, 1σ, n= 5) obtained using 21.2 mL of cylinder stabilizer highly agreed with that of 0.05384 ± 0.74‰ (1σ, n= 5) using the commercially available “squid” stabilizer. The analytical efficiency of the 21.2 mL of cylinder stabilizer was then compared to that of cubic shape stabilizer (18.5 mL) and ball shape stabilizer (14.1 mL). Results showed that there were no significant differences of the obtained 206Pb/238U ages using stabilizers with volume in the range of 14.1–21.2 mL. But both cubic and ball shape stabilizers exhibited washout time over 270 s. We also studied the particle filter effect of the stabilizers by packing the 21.2 mL of cylinder stabilizer with 1.0 g of stainless wire. Despite the average 206Pb/238U age deviation was only − 0.81%, spiky signals occasionally occurred which might be ascribed to the use of a nanosecond laser and relatively low density of stainless wire in the stabilizer. This study confirmed that an empty stabilizer with volume of 21.2 mL and cylinder shape was preferred to produce smoothing signals. The improved analytical accuracy of zircon U–Pb dating using such a stabilizer ensured the future application to trace element analysis by LA-ICP-QMS.

The original version of this Article contained an error in the author affiliations. Affiliation number 4 incorrectly read “Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Disease, Tianjin Institute of Digestive Disease”. It should be “Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300052, China”.

Objective:To investigate the long-term prognostic factors of CBFB-MYH11-positive acute myeloid leukemia in low、 intermediate risk patients.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

Previous studies have suggested that IKZF1gene deletions are associated with an adverse prognosis in acute lymphoblastic leukemia (ALL). However, the prognostic value of IKZF1deletions in adult common B-cell ALL (Com-B ALL) has not been well-defined, especially in the context of different post-remission therapies. The objectives of this study were to evaluate the prognostic role of IKZF1deletions in adult Com-B ALL.

Whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) or imatinib should be first-line therapy for childhood chronic myelogenous leukemia in the chronic phrase (CML-CP) is controversial. This study compared imatinib monotherapy and allo-HSCT for the management of CML-CP in pediatric patients.This was a retrospective study of children (aged <18 years) with CML-CP, treated between January 2006 and September 2012 at a hospital in China. Patients were treated with imatinib (260 mg/m2 body surface area) or allo-HSCT. Overall survival (OS), event-free survival (EFS) and adverse events (AEs) were compared.62 patients (40 males, 22 females) were enrolled: 41 received imatinib, and 21 received allo-HSCT. Median follow-up in the imatinib and allo-HSCT groups was 29 and 56 months, respectively. Imatinib was well tolerated. In the imatinib group, the cumulative complete cytogenetic response (CCyR) and major molecular response (MMR) at 24 months were 96.6% (95%CI, 93.3–99.9%) and 85.6% (95%CI, 78.5–92.7%), respectively; patients achieved CCyR and MMR at a median of 3 and 6 months, respectively. In the allo-HSCT group, allografts were from an HLA-matched sibling (n=3), an HLA mismatched/haploidentical familial donor (n=15) or an unrelated donor (n=3). Twelve patients (57.1%) developed acute graft-versus-host disease (grades 2–6 in 7 patients), and 5 deaths were reported. 5-year OS in the imatinib and allo-HSCT groups was 97.1±2.9% and 73.7±10.3% (P=0.032), respectively, while 5-year EFS was 92.5±4.2% and 63.8±11.1% (P=0.041), respectively.Treatment with imatinib yielded satisfactory cytogenetic and molecular responses, and superior 5-year OS and EFS to allo-HSCT.No relevant conflicts of interest to declare.

Prolonged thrombocytopenia is a common complication after allogeneic hematopoietic stem cell transplantation(allo-HSCT),which is associated with a high mortality and poor prognosis. The aim of this study was to assess the impact of the CD8+CX3CR1+ T cells on the development and maturation of megakaryocytes in patients with the prolonged thrombocytopenia after allo-HSCT in order to identify the risk factors related to thrombocytopenia after allo-HSCT.

No relevant conflicts of interest to declare.

Whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) or imatinib should be first-line therapy for childhood chronic myelogenous leukemia in the chronic phrase (CML-CP) is controversial. This study compared imatinib monotherapy and allo-HSCT for the management of CML-CP in pediatric patients.

Recent results from our prospective multi-center study identified patients with t (8; 21) AML as high-risk according to their MRD status after the second consolidation chemotherapy and allo-HSCT can benefit this part of patients; however, the relapse rate was reported to be 22% even after allo-HSCT for those high-risk patients. To date, there have been no studies to answer the question of whether the specific fusion gene, RUNX1/RUNX1T1 can be used to further distinguish between patients with low and high risks of relapse in allo-HSCT setting, just like the already established standard for MRD measurement in CML and APL.

Recent results from our prospective multi-center study identified patients with t (8; 21) AML as high-risk according to their MRD status after the second consolidation chemotherapy and allo-HSCT can benefit this part of patients; however, the relapse rate was reported to be 22% even after allo-HSCT for those high-risk patients. To date, there have been no studies to answer the question of whether the specific fusion gene, RUNX1/RUNX1T1 can be used to further distinguish between patients with low and high risks of relapse in allo-HSCT setting, just like the already established standard for MRD measurement in CML and APL.Sixty consecutive AML patients with t (8; 21) and identified as high-risk according to the criteria from our recently published report patients who received allo-HSCT were enrolled between January 2006 and January 2013. Serial MRD monitoring by RQ-PCR post HSCT was done. The impact of MRD monitoring on transplant outcomes was assessed.A > 3 log reduction at 1 month after HSCT in RUNX1/RUNX1T1 transcripts from diagnosis, is associated with 2-year CIR of 17% in the 88% of patients achieving it, compared with 43% in the remaining (p=.02). A > 3 log reduction at 2 months after HSCT in transcripts from diagnosis, is associated with a CIR of 9% and LFS of 66% in the 86% of patients achieving it, compared with CIR of 100% and LFS of 0% in the remaining (both p<.001). A > 3 log reduction at 3 months after HSCT in RUNX1/RUNX1T1 transcripts from diagnosis, is associated with a CIR of 11% and LFS of 73% in the 78% of patients achieving it, compared with CIR of 44% and LFS of 0% in the remaining (both p<.001). Of the 60 patients analyzed, 28 patients had positive MRD, occurring at a median of 110 days (30-540 days) after transplant. The predictive value of sequential monitoring could be demonstrated in 8 patients culminating in clinical relapse (representing 73% of all relapsing patients). The median time from MRD positivity in BM to morphological relapse was 95 days (range, 33-140 days).A > 3 log reduction at the first 3 months after HSCT in RUNX1/RUNX1T1 transcripts from diagnosis is highly prognostic. We conclude that MRD monitoring by RQ-PCR at regular early time points post HSCT in t (8; 21) AML allows further identification of patients at high risk of relapse even after allo-HSCT and could now be incorporated in clinical trials to evaluate the role of risk directed prophylactic/preemptive therapy. This work was partly supported by The Key Program of National Natural Science Foundation of China £¨Grant No. 81230013£©, Beijing Municipal Science & Technology Commission (No.Z121107002812033) and Bejing Municipal Science & Technology Commission£¨No.Z111107067311070).No relevant conflicts of interest to declare.

Current studies suggest that monitoring the minimal residual disease (MRD) of patients with malignant hematological disease after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is helpful for screening patients at high risk of relapse. WT1 and leukemia-associated aberrant immune phenotypes (LAIPs) were the major MRD parameters used to predict leukemia relapse after allo-HSCT. The aim of this study was to first evaluate the clinical value of various positive MRD standards for accurately predicting relapse based on WT1 and flow cytometry (FCM) data in a large sample of adult patients with actue leukemia (AL) in a single transplant center.In total, 824 AL patients treated with non-T-cell-depleted allo-HSCT at the Peking University Institute of Hematology from January 1, 2006 to November 30, 2011 were enrolled in this study. BM samples from patients were obtained at regular time points: +1 month, +2 months, +3 months, +4.5 months, +6 months, +9 months, +12 months and every 6 months thereafter for the MRD investigation after HSCT. WT1 expression was evaluated using TaqMan-based RQ-PCR technology and LAIPs were detected using 4/7-color FCM. At least one positive MRD marker, including WT1 or LAIP, was detected before transplantation in 90.8% (748 of 824) of the subjects. Positive FCM could be found in all 748 patients. Both FCM+ and WT1+ were detected before transplantation in 58.7% (484/824) of subjects. We compared the sensitivity and specificity of diverse, multiple-criteria MRD forecasting standards including one WT1+, two consecutive WT1+, one FCM+, two consecutive FCM+, concurrent WT1+ & FCM+, concurrent WT11.0+ & FCM+, MRDco+ and MRDco1.0+, based on WT1 and FCM assays.Higher sensitivity was achieved without a loss of specificity in total 824 patients as well as in 748 patients with WT1+ or FCM+ before transplant when MRDco+ was used as the positive MRD standard (Table 1). Similar results were observed, even in 484 patients with acute myeloid leukemia (AML, n=308) and acute lymphoblastic leukemia (ALL, n=176) who had both abnormal WT1 and LAIPs values before transplant (Table 1). A multivariate analysis that included age, sex, disease status (CR1/CR2), donor type, number of chemotherapy courses before CR1, and MRD status (including the different MRD standards mentioned above) after transplantation showed that MRDco+ was an independent risk factor to predict leukemia relapse after allo-HSCT; it had the most powerful contribution to leukemia recurrence after transplant in both AML (HR=12.54, 95% CI: 7.01–22.42, P<0.001) and ALL (HR=12.84, 95% CI: 6.05–27.25, P<0.001) compared with other MRD standards.The combined use of FCM and WT1 monitoring were able to distinguish between patients with low and high risk of relapse. Diverse standards of positive MRD raised in this work were conductive to guide different interventive measures. Further studies should focus on exploring the new better parameters with both high sensitivity and specificity in predicting the recurrence of leukemia after allo-HSCT.No relevant conflicts of interest to declare.

Using neonatal NOD/SCID/IL2rγnull xenotransplantation model, we previously demonstrated that CD34+CD38+CD19+ cells as well as CD34+CD38−CD19+ cells have the capacities to initiate B-precursor ALL (B-ALL) in vivo and to self-renew, that is, leukemia initiating cells(LICs) are enriched in the CD34+CD19+phenotype in human B-ALL (Kong Y et al. Leukemia 2008; 22: 1207–1213). Nevertheless, in order to distinguish B-ALL initiating cells from their normal compartment, further markers have to be identified. CD58 (lymphocyte function–associated antigen 3), a cell surface adhesion molecule binding to CD2, plays a critical role in the attachment of cytotoxic T lymphocytes and non-specific killer cells to their targets. Recent data give evidence that diffuse large B cell lymphoma patients with poor expression of CD58 appear to be more aggressive by escaping from immune-surveillance of the host. However, the prognostic relevance of CD58 expression on B-ALL initiating cells is largely unknown.To investigate the expression profile of CD58 on CD34+CD19+B-ALL initiating cells. To evaluate the prognostic significance of CD58 expression on LICs in human B-precursor ALL.Using a cohort of 139 patients (including pediatric and adult patients) with CD34+ B-ALL, the expression profile of CD58 on LICs(CD34+CD19+ phenotype) were examined by multicolor flow cytometry (FCM) at diagnosis. A total of 1,050,000 events were routinely collected. More than 20% of LICs with CD58 expression were defined as CD58-positive LICs (CD34+CD19+CD58+ phenotype, abbreviated by CD58+LICs), all other cases were defined as CD58-negtive LICs (CD34+CD19+CD58−phenotype, abbreviated by CD58−LICs). Furthermore, the impact of CD58−LICs at diagnosis on the clinical outcome was prospectively investigated. The study was approved by the Ethics Committee of Peking University People's Hospital and written informed consent was obtained from all subjects.Among the newly diagnosed B-ALL patients, 119 cases were detected with CD58+LICs and the remaining 20 cases with CD58−LICs. The expression of CD58 on LICs at diagnosis was inversely related to the age, WBC at diagnosis and NCCN risk group of the B-ALL patients (P=0.002, P=0.015 and P=0.009, respectively). CD58+LICs group had a higher complete remission(CR) rate after one course induction than CD58−LICs group (87.39% vs. 65.00%, P=0.019).Cumulative incidence of relapse (CIR) at 2-year in the CD58+LICs group was significantly lower than that in the CD58−LICs group (18.20% ± 0.15% vs. 72.00% ± 1.30%, P<0.0001). CD58+LICs group resulted in superior survival compared to CD58−LICs group (2-year disease-free survival(DFS), 77.95% ± 4.36% vs. 28.00% ± 10.58%, P<0.0001; 2-year overall survival(OS), 75.61% ± 5.53% vs. 42.4% ± 11.50%, P = 0.0016). Multivariate analysis revealed CD58−LICs at diagnosis as independent risk factor affecting relapse (HR=3.413, P=0.001) and DFS (HR=2.857, P=0.004) in B-ALL patients. By summing up the risk factors(RF) defined as CD58 status on LICs (CD58+LICs=0,CD58−LICs=1),age(<18 years=0,≥18 years=1) and NCCN risk group (Standard risk=0, High risk=1), two prognostic groups (Low risk group: RF≤1;High risk group: RF>1)could be discriminated, which differed significantly with regard to 2-year CIR(9.18%±0.14% vs. 49.94%±0.67%, P<0.0001), 2-year DFS (90.82%±5.65% vs. 39.83%±7.97%, P<0.0001) and 2-year OS(91.21%±3.87% vs. 45.27%±7.89%, P<0.0001), respectively.CD58-negtive leukemia initiating cells at diagnosis independently correlate with unfavorable prognosis. Combined analysis of CD58 status on CD34+CD19+leukemia initiating cells at diagnosis, age and NCCN risk group may help to optimize currently available prognostic stratification model in B-ALL.This work was supported by grants from National Natural Science Foundation of China (30800483) and Beijing Municipal Science and Technology Program (Z111107067311070).No relevant conflicts of interest to declare.

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