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To address the problem of the low accuracy of transverse velocity field measurements for small targets in high-resolution solar images, we proposed a novel velocity field measurement method for high-resolution solar images based on PWCNet. This method transforms the transverse velocity field measurements into an optical flow field prediction problem. We evaluated the performance of the proposed method using the Ha and TiO datasets obtained from New Vacuum Solar Telescope (NVST) observations. The experimental results show that our method effectively predicts the optical flow of small targets in images compared with several typical machine- and deep-learning methods. On the Ha dataset, the proposed method improves the image structure similarity from 0.9182 to 0.9587 and reduces the mean of residuals from 24.9931 to 15.2818; on the TiO dataset, the proposed method improves the image structure similarity from 0.9289 to 0.9628 and reduces the mean of residuals from 25.9908 to 17.0194. The optical flow predicted using the proposed method can provide accurate data for the atmospheric motion information of solar images. The code implementing the proposed method is available on https://github.com/lygmsy123/transverse-velocity-field-measurement., 14 pages, 10 figures, 4 tables. Accepted for publication in Research in Astronomy and Astrophysics

Prolonged isolated thrombocytopenia (PIT) is a common complication after umbilical cord blood transplantation (UCBT). However, data on PIT prediction and impacts on transplantation outcomes for UCBT patients are rare. We retrospectively analyzed 244 patients with hematological malignancies who received single-unit UCBT at the First Affiliated Hospital of USTC between August 2018 and December 2019. Among them, PIT occurred in 49 recipients, with a crude incidence of 20.1%. In the PIT patients, the 2-year cumulative incidence of transplant-related mortality (TRM) was significantly higher, and the probabilities of 2-year overall survival, leukemia-free survival and graft-versus-host disease (GVHD)-free relapse-free survival were significantly poorer (57.1% vs. 88.6%; 53.1% vs. 81.9%; 22.4% vs. 59.8%; p

Background: Our previous studies have demonstrated that Luks-PV have good anti-leukemia ability effects and could possibly be a promising therapy for adult acute myeloid leukemia (AML). Aberrant over-expression of HOXA9 is a prominent feature of AML driven by multiple oncogenes, and therapeutic degrading of HOXA9 may be an effective treatment strategy in AML. This paper focused on the Luks-PV-regulating autophagy pathway, aiming to investigate the role of Luks-PV in mixed-lineage leukemia (MLL)-rearranged AML. Methods: The data of leukemia patients were downloaded from the gene expression profiling of TCGA datasets. Taking primary AML and THP-1 cells as the model system in vitro, Luks-PV-inhibited cell proliferation was determined by CCK‐8 and flow cytometry assays. The role of Luks-PV in autophagy regulation was analyzed using immunoblotting, transfection and immunofluorescence.Results: HOXA9 was over-expressed and associated with a poor prognosis in AML patients bearing MLL rearrangement. After the application of pharmacologic inhibitors of autophagy, Luks-PV induced cytotoxic autophagy in AML cells, as suggested by biochemical and microscopy results. HOXA9 molecules were detectable within autophagosomes after Luks-PV treatment, indicating that autophagy induction accounted for the degradation of HOXA9. Moreover, Luks-PV-induced HOXA9 downregulation inhibited AML cell proliferation, suggesting that HOXA9 could be degraded through Luks-PV-induced autophagy.Conclusion: Luks-PV suppresses AML cell proliferation by inducing HOXA9 degradation.

Bromodomain-containing protein 4 (BRD4) overexpression promotes ovarian cancer progression, and represents an important therapeutic oncotarget. This current study identified microRNA-765 (miR-765) as a novel BRD4-targeting miRNA. We showed that miR-765 directly associated with and silenced BRD4. In primary ovarian cancer cells and established cell lines (SKOV3 and CaOV3), ectopic overexpression of miR-765 inhibited cancer cell proliferation, migration and invasion, and induced apoptosis activation. In contrast, miR-765 inhibition by its anti-sense induced BRD4 upregulation to promote ovarian cancer cell proliferation, migration and invasion. Significantly, miR-765 overexpression-induced anti-ovarian cancer cell activity was largely attenuated by restoring BRD4 expression through an UTR-null BRD4 construct. Moreover, CRISPR/Cas9-induced BRD4 knockout (KO)inhibited proliferation and activated apoptosis in ovarian cancer cells. BRD4 KO in ovarian cancer cells abolished the functional impact of miR-765. miR-765 expression levels were downregulated in human ovarian cancer tissues and cells, correlating with the upregulation of BRD4 mRNA. Collectively, BRD4 silencing by miR-765produces significant anti-ovarian cancer cell activity. miR-765 could be further tested for its anti-ovarian cancer potential.

Acute myeloid leukaemia (AML) is a frequently fatal malignant disease of haematopoietic stem and progenitor cells. The molecular and phenotypic characteristics of AML are highly heterogeneous. Our previous study concluded that CaMKIIγ was the trigger of chronic myeloid leukaemia progression from the chronic phase to blast crisis, but how CaMKIIγ influences AML stem-like cells remains elusive. In this study, we found that CaMKIIγ was overexpressed in AML patients and AML cell lines, as measured by qRT-PCR and Western blot assays. Moreover, CaMKIIγ decreased when the disease was in remission. Using an shRNA lentivirus expression system, we established CaMKIIγ stable-knockdown AML cell lines and found that knockdown of CaMKIIγ inhibited the viability and self-renewal of AML stem-like cell lines. Additionally, the ratio of CD34 + AML cell lines decreased, and CaMKIIγ knockdown induced the downregulation of Alox5 levels. We further detected downstream molecules of the Alox5/NF-κB pathway and found that c-myc and p-IκBα decreased while total IκBα remained normal. In conclusion, our study describes a new role for CaMKIIγ as a stem-like cell marker that is highly regulated by the Alox5/NF-κB pathway in AML stem-like cells. CaMKIIγ can participate in the viability and self-renewal of AML stem-like cells by regulating the Alox5/NF-κB pathway.

N6-methyladenosine (m6A) demethylase fat mass and obesity-associated gene(FTO), previously recognized to be related with obesity and diabetes, was gradually discovered to be dysregulated in multiple cancers and plays an oncogenic or tumor-suppressive role. However, the specific expression and pro- or anti-cancer role of FTO in various cancers remained controversial. In this review, through summarizing the available literature, we found that FTO single nucleotide polymorphisms (SNPs) were closely related with cancer risk. Additionally, the dysregulation of FTO was implicated in multiple biological processes, such as cancer cell apoptosis, proliferation, migration, invasion, metastasis, cell-cycle, differentiation, stem cell self-renewal and so on. These modulations mostly relied on the communications between FTO and specific signaling pathways, including PI3K/AKT, MAPK and mTOR signaling pathways. Furthermore, FTO had great potential for clinical application by serving as a prognostic biomarker.

Image-based deep learning method for plant disease diagnosing is promising but relies on large-scale dataset. Currently, the shortage of data has become an obstacle to leverage deep learning methods. Few-shot learning can generalize to new categories with the supports of few samples, which is very helpful for those plant disease categories where only few samples are available. However, two challenging problems are existing in few-shot learning: (1) the feature extracted from few shots is very limited; (2) generalizing to new categories, especially to another domain is very tough. In response to the two issues, we propose a network based on the Meta-Baseline few-shot learning method, and combine cascaded multi-scale features and channel attention. The network takes advantage of multi-scale features to rich the feature representation, uses channel attention as a compensation module efficiently to learn more from the significant channels of the fused features. Meanwhile, we propose a group of training strategies from data configuration perspective to match various generalization requirements. Through extensive experiments, it is verified that the combination of multi-scale feature fusion and channel attention can alleviate the problem of limited features caused by few shots. To imitate different generalization scenarios, we set different data settings and suggest the optimal training strategies for intra-domain case and cross-domain case, respectively. The effects of important factors in few-shot learning paradigm are analyzed. With the optimal configuration, the accuracy of 1-shot task and 5-shot task achieve at 61.24% and 77.43% respectively in the task targeting to single-plant, and achieve at 82.52% and 92.83% in the task targeting to multi-plants. Our results outperform the existing related works. It demonstrates that the few-shot learning is a feasible potential solution for plant disease recognition in the future application.

Background：Juvenile myelomonocytic leukemia (JMML) is a rare hematological malignancy in young children and can only be cured through the allogeneic stem cell transplantation. Procedure：We have retrospectively analyzed the outcomes of nine children with JMML after unrelated cord blood transplantation (UCBT). Results：Eight patients who have received a myeloablative conditioning regimen of fludarabine (FLU), busulfan (BU), and cyclophosphamide (CY) have gotten engraftment. None of the nine patients has relapsed following initial UCBT. Six patients are still alive and in complete remission after UCBT with a median observation time of 43 months (range: 10–80 months). The 5-year overall (OS) and event-free (EFS) survival rates are 77.8% and 66.7%, respectively. Conclusions：This study shows that UCBT with FLU–BU–CY conditioning regimen can represent a suitable option for children with JMML.

BACKGROUND Juvenile myelomonocytic leukemia (JMML) is a rare hematological malignancy in young children and can only be cured through the allogeneic stem cell transplantation. PROCEDURE We have retrospectively analyzed the outcomes of nine children with JMML after unrelated cord blood transplantation (UCBT). RESULTS Eight patients who have received a myeloablative conditioning regimen of fludarabine (FLU), busulfan (BU), and cyclophosphamide (CY) have gotten engraftment. None of the nine patients has relapsed following initial UCBT. Six patients are still alive and in complete remission after UCBT with a median observation time of 43 months (range: 10-80 months). CONCLUSIONS This study shows that UCBT with FLU-BU-CY conditioning regimen can represent a suitable option for children with JMML.

Aberrant over-expression of HOXA9 is a prominent feature of AML driven by multiple oncogenes, thus therapeutic degradation of HOXA9 by autophagy may be an effective treatment strategy for AML. PVL is a pore forming cytotoxin secreted by Staphylococcus aureus, and it is composed of two subunits - LukS-PV and LukF-PV. Here, we show that LukS-PV can stimulate the conversion of LC3-I to LC3-II in AML cells in a concentration-dependent manner, and autophagic vacuoles can be found in LukS-PV-treated THP-1 cells. Furthermore, we find that an accumulation of LC3-positive structures in AML cells exposed to LukS-PV, indicating that an increased autophagic flux were formed. Therefore, LukS-PV induced autophagy of AML cells. We also demonstrated that LukS-PV could regulate the expression of HOXA9 at the protein level. HOXA9 molecules were detected in autophagosomes after LukS-PV treatment, indicating that autophagy induction accounted for the degradation of HOXA9.

Background: CD19-directed chimeric antigen receptor (CAR) T cells have substantial benefit in the treatment of patients with B-cell malignancies. However, despite encouraging therapeutic efficiency, there is limited overall response rate when anti-CD19 CAR-T cells are used to treat patients with relapsed and refractory (R/R) B cell lymphomas. Therefore, it further investigation is urgently needed to improve treatment efficacy. Method: A combined treatment protocol of CAR-T cell with decitabine (DAC) to treat B cell lymphoma was developed and tested on lymphoma cell lines first, and then efficacy and the underlying mechanism were investigated. After ethical approval was granted, the combined treatment protocol was applied to treat two patients with R/R B-cell lymphomas. Results: CAR-T cells were prepared successfully, and they recognized CD19 antigen expressed on lymphoma cell lines specifically. Cell-line studies also showed that CD19 antigen expression was increased by DAC pretreatment, and the function of CAR-T cells was not compromised. The cell-line study further demonstrated that lymphoma cells pretreated by DAC responded more to the treatment of CAR-T cells. Two patients with R/R B cell lymphoma were pretreated with DAC then treated with CAR-T, and both achieved complete remission (CR). Conclusions: The epigenetic modifying drug DAC increases expression of the surface antigen CD19 on lymphoma cells. The DAC pretreatment protocol may lead patients with B cell lymphoma to be more susceptible to adoptive transfer of anti-CD19 CAR-T cells treKeywordsatment.

The human insulin-like growth factor 2 (IGF2) mRNA binding proteins 2 (IGF2BP2/IMP2) is an RNA-binding protein that regulates multiple biological processes. Previously, IGF2BP2 was thought to be a type 2 diabetes (T2D)-associated gene. Indeed IGF2BP2 modulates cellular metabolism in human metabolic diseases such as diabetes, obesity and fatty liver through post-transcriptional regulation of numerous genes in multiple cell types. Emerging evidence shows that IGF2BP2 is an N6-methyladenosine (m6A) reader that participates in the development and progression of cancers by communicating with different RNAs such as microRNAs (miRNAs), messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs). Additionally, IGF2BP2 is an independent prognostic factor for multiple cancer types. In this review, we summarize the current knowledge on IGF2BP2 with regard to diverse human metabolic diseases and its potential for cancer prognosis.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for most of acute myeloid leukemia (AML) patients. But relapse remains the leading cause of mortality after transplant. Ex vivo expanded allogeneic CD4- and CD8- double negative T cells (allo-DNTs) effectively target AML cells without attacking normal tissues in preclinical models. In this first-in-human phase I/IIa trial, twelve patients with relapsed AML after allo-HSCT were treated with allo-DNTs. Nine patients had hematological relapse, 2 with molecular relapse, and 1 had both molecular and extramedullary relapse. The median times from transplant to relapse and relapse to DNT therapy were 10 months (3-18 months) and 4.7 months (1.75-11.7 months), respectively. At the time of DNT-treatment, 11/12 patients had active or residual disease. After lymphodepleting preconditioning, patients received allo-DNTs in three dose cohorts (5x107-4x108/kg). None of the patients developed graft-versus-host disease or > grade 2 DNT treatment-related toxicity; hence, the maximum tolerated dose was not reached. One patient withdrew from this trial. The initial response was observed in 7 out of 11 patients, where 4 patients achieved complete remission (CR), 2 achieved CR with incomplete hematologic recovery, and 1 achieved partial remission. Five patients remain alive and 4 are in continuing CR 374 to 609 days after DNT-treatment. The predicted 1-year overall survival after DNT treatment is 45.5% (95% CI, 16.7%-70.7%). Collectively, the study supports the feasibility, safety, and potential efficacy of allo-DNTs as a new treatment option for patients with relapsing/relapsed AML after allo-HSCT. Trial Registration: The trial was registered on the Chinese Clinical Trial Registry (ChiCTR-IPR-1900022795). Funding: This work was supported by the National Natural Science Foundation of China (grant # 81670165), International Cooperation Projects in Anhui Province (grant # 1804b06020352), the Fundamental Research Funds for the Central Universities (grants # WK9110000001 and WK9110000060), the Canadian Cancer Society Impact Grant (grant # 704121), Canadian Institutes of Health Research (grant # 419699), the Leukemia & Lymphoma Society (grant #R6509-18) and WYZE Biotech Inc. Declaration of Interest: LZ is a co-inventor on several DNT cell technology related patents and intellectual properties (IPs), received a grant and consulting fees from WYZE Biotech Co. Ltd. WYZE Biotech Co. Ltd licensed the Chinese right for one of the patents; and LZ owns shares in WYZE Biotech Co. Ltd.. LY, JL, and ADS are co-inventor on DNT cell technology related patents/IPs. LY, ZX, MW and PT own shares in WYZE Biotech Co., Ltd and are employees of WYZE Biotech Co., Ltd. MISSING REMAINING AUTHORS Ethical Approval: This study protocol was approved by Chinese Ethics Committee of Registering Clinical Trials. Written informed consent was obtained from all the patients or guardians in accordance with the Declaration of Helsinki.

Long-term herbicide application may facilitate the adaptive evolution of weed populations. With长期进行除草剂药效试验可能会导致田间杂草种群发生适应性进化。本研究在安徽南陵县除草剂药效试验专用稻田中采集了1个稗草种群A,并以从常规稻田采集的3个稗草种群为对照,开展同质园栽培试验。结果表明: 与3个对照种群相比,A种群稗草植株的单株种子产量显著减少,种子千粒重显著增加,幼苗生长速率显著加快,结实分蘖数显著增多,生育期显著缩短;A种群稗草成株的株高、生物量及对除草剂五氟磺草胺的敏感性均显著降低。A种群稗草幼苗3～4叶期时经五氟磺草胺推荐剂量2倍量(有效成分60 g·hm

Acute graft-versus-host disease (aGVHD) is a complication of allogeneic hematopoietic stem cell transplantation. Ras-related protein 1A (RAP1A) has been recently identified as a novel oncoprotein in several human malignancies. However, its specific role in aGVHD remains unclear.To study the role of RAP1A in the pathogenesis of aGVHD.Study participants included six patients with grade 2-4 aGVHD, 13 patients with grade 1 aGVHD, 11 patients without aGVHD, and 12 healthy people. The expression level of RAP1A in whole cells was detected by western blot and qRT-PCR. The proportions of CD4We found the level of RAP1A was higher in patients than in healthy individuals. A negative correlation was noted between RAP1A and the number of Treg cells. In addition, the level of IL-10 in patients with grade 2-4 aGVHD was significantly lower than that in healthy donors, however, the level of TNF-ɑ in patients with grade 2-4 aGVHD was higher. Furthermore, we found a negative correlation between levels of IL-10 and RAP1A, and a positive correlation between TNF-ɑ and RAP1A.The expression of RAP1A in patients with aGVHD was significantly increased, and shows potential as a target for the prevention and treatment of aGVHD.

Background: Our previous studies have demonstrated that Luks-PV have good anti-leukemia ability effects and could possibly be a promising therapy for adult acute myeloid leukemia (AML). Aberrant over-expression of HOXA9 is a prominent feature of AML driven by multiple oncogenes, and therapeutic degrading of HOXA9 may be an effective treatment strategy in AML. This paper focused on the Luks-PV-regulating autophagy pathway, aiming to investigate the role of Luks-PV in mixed-lineage leukemia (MLL)-rearranged AML. Methods: The data of leukemia patients were downloaded from the gene expression profiling of TCGA datasets. Taking primary AML and THP-1 cells as the model system in vitro, Luks-PV-inhibited cell proliferation was determined by CCK‐8 and flow cytometry assays. The role of Luks-PV in autophagy regulation was analyzed using immunoblotting, transfection and immunofluorescence.Results: HOXA9 was over-expressed and associated with a poor prognosis in AML patients bearing MLL rearrangement. After the application of pharmacologic inhibitors of autophagy, Luks-PV induced cytotoxic autophagy in AML cells, as suggested by biochemical and microscopy results. HOXA9 molecules were detectable within autophagosomes after Luks-PV treatment, indicating that autophagy induction accounted for the degradation of HOXA9. Moreover, Luks-PV-induced HOXA9 downregulation inhibited AML cell proliferation, suggesting that HOXA9 could be degraded through Luks-PV-induced autophagy.Conclusion: Luks-PV suppresses AML cell proliferation by inducing HOXA9 degradation.

In order to weaken the influences of system uncertainties on the coordinated tracking control performance of the speed and tension system of the reversible cold strip rolling mill, a backstepping sliding model control strategy is proposed based on the extended state observers (ESOs). First, the ESOs are constructed to dynamically observe the system's unmatched uncertainties, which effectively improve the system's tracking control precision. Next, based on the backstepping control and the tracking differentiators (TDs), the integral sliding mode controllers (ISMCs) for the speed and tension system of the reversible cold strip rolling mill are designed, which solve the "differential explosion" problem of conventional backstepping control, and improve the robust stability of the system, Finally, simulation research is carried out on the speed and tension system of a 1422 mm reversible cold strip rolling mill by using actual data, and the results show the validity of the proposed control strategy.

Background We previously reported that LukS-PV induces apoptosis in human acute myeloid leukaemia (AML) cells. Furthermore, SET8 is a member of the SET domain-containing methyltransferase family and overexpressed in numerous tumours, including AML and indicated a poor prognosis. However, it is unclear whether LukS-PV induce apoptosis via SET8. In current study, we aimed to investigate the regulatory mechanisms of SET8 and effects on AML cells under the LukS-PV.Methods Flow cytometry was performed to detect apoptosis in AML primary blasts/cell lines treated with LukS-PV and invasion of AML cells in vivo. The expression of SET8 was quantified through reverse-transcription PCR and western blotting. Chromatin-immunoprecipitation (ChIP) sequencing and bioinformatic methods was performed to explore transcriptional target genes which regulated by SET8-H4K20me1 axis. All experiments were performed in triplicate, and all statistical analyses were conducted using SPSS 16.0.Results In this research, we found that LukS-PV induce cell apoptosis in vitro and inhibit cell invasion in vivo. Our results further confirmed SET8 and H4K20me1 were downregulated in LukS-PV-treated AML cells. Furthermore, we confirmed that LukS-PV induced apoptosis via downregulating SET8/H4K20me1. Finally, Genome-wide analysis identified PIK3CB is the target gene for cell apoptosis mediated by SET8/H4K20me1. In a nutshell, LukS-PV induces apoptosis via the PIK3CB/PI3K/AKT/FOXO1 signal pathway by targeting SET8.Conclusions The present results indicate that LukS-PV induces apoptosis in AML cells by downregulating SET8 and regulating downstream molecular targets, suggesting that SET8 is a potential target for AML therapy using LukS-PV for anti-leukaemia treatment.

What is known and objective Many refractory/relapsed haematological malignancies, in non-remission state, still have poor prognosis even after allogeneic haematopoietic stem cell transplantation. Recently, decitabine or umbilical cord blood transplantation (UCBT) seemed to be effective in these patients. However, few studies have added decitabine to myeloablative conditioning regimens for UCBT in patients with haematological malignancies not in remission. Therefore, the objective was to evaluate the clinical outcomes of patients with refractory/relapsed acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) using decitabine as part of a myeloablative conditioning regimen prior to salvaged unrelated UCBT at our centre. Methods We enrolled 20 consecutive patients with refractory/relapsed AML/MDS between 2013 and 2018. All patients were in non-remission state before transplantation. All transplants were performed with decitabine as part of the myeloablative conditioning regimen, which was decitabine + fludarabine/busulfan/cyclophosphamide. Results and discussion All patients achieved neutrophil and platelet engraftment. Incidence of grade III/IV acute graft-vs-host disease (GVHD) was 20.0%, which was also decreased compared to non-decitabine group (P = .025). The median follow-up time after UCBT was 29 months (range 14-64 months). The 2-year probability of GVHD-free relapse-free survival (GRFS) was higher in the decitabine group. Univariate showed that the decitabine group was associated with a higher GRFS than the non-decitabine group. The estimated probability of overall survival and relapse was 55% and 20.0%, respectively. What is new and conclusions Our results suggest that addition of decitabine as part of the myeloablative conditioning regimen prior to UCBT for refractory/relapsed AML/MDS in patients who are not in remission is safe and might be an effective treatment option.

Background: Histone modifiers contribute to leukaemia pathogenesis. LukS-PV is a component of the Panton-Valentine leukocidin (PVL) cytotoxin secreted by Staphylococcus aureus. We previously reported that LukS-PV induces apoptosis in human acute myeloid leukaemia (AML) cells (THP-1 and HL-60). However, it is unclear whether LukS-PV exerts biological effects through epigenetic regulation. We aimed to investigate the epigenetic regulatory mechanisms underlying the effects of LukS-PV. Methods: SET8 expression was quantified through reverse-transcription PCR and western blotting in patient-derived AML cells. To determine whether LukS-PV influences apoptosis and proliferation via SET8, AML cell lines HL-60 and NB-4 were treated with LukS-PV, and SET8 expression was quantified. Chromatin-immunoprecipitation (ChIP) was performed to determine whether LukS-PV regulates H4K20me1 via SET8, and transcriptional targets were determined through ChIP-seq and bioinformatic methods. Findings: Methyltransferase SET8 was upregulated in primary AML blasts and downregulated in LukS-PV-treated AML cells HL-60 and NB4. LukS-PV induced apoptosis and inhibited proliferation by downregulating SET8. Furthermore, LukS-PV regulated H4K20me1 through SET8. Genome-wide analysis identified PIK3CB as the direct target of LukS-PV-mediated H4K20me1. Furthermore, PIK3CB inhibitor GSK2636771 induced apoptosis and inhibited proliferation in HL-60 and NB4 cells. Moreover, LukS-PV induced apoptosis and inhibited proliferation in primary AML blasts. Conclusions: The present results indicate that LukS-PV induces apoptosis and inhibits proliferation in AML cells by downregulating SET8 and regulating downstream molecular targets, suggesting that SET8 is a potential target for AML therapy using LukS-PV for anti-leukaemia treatment. Funding Statement: This work was supported by the Anhui Natural Science Foundation(Grant No.1808085QH259), the Fundamental Research Funds for Central Universities (WK9110000107) and National Natural Science Foundation of China (Grant No.81572065). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: This study was approved by the Ethics Committee and Institutional Review Board of University of Science and Technology of China, Anhui, China (Approval number: 2019-N(H)-101).

Background Several studies have indicated that chimeric antigen receptor T-cell (CAR-T) therapy followed by allogeneic hematopoietic stem cell transplantation is beneficial for relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Whether consolidative unrelated cord blood transplantation (UCBT) is suitable in R/R B-ALL after CAR-T therapy remain uncertain. Objective We aimed to assess the efficacy and safety of CAR-T therapy before UCBT for children and young adults R/R B-ALL patients. Study design : We retrospectively analyzed 43 R/R B-ALL and under 18 years patients who underwent single-unit UCBT at the First Affiliated Hospital of University of Science and Technology of China (USTC) between February 2012 and November 2020. Among them, 21 patients achieved complete remission (CR) following CAR-T therapy before UCBT (the CAR-T group), and the remaining 22 patients remained non-remission (NR) without prior CAR-T therapy before UCBT (the NR group). The clinical outcomes between two groups were analyzed. Results : The median time from CAR-T therapy to UCBT was 62 (range,42 to 185) days. There were no significant differences in the incidences of grade II-IV, III-IV acute graft-versus-host disease (GVHD) and 2-year extensive chronic GVHD between the two groups. Compared with the NR group, a lower 2-year cumulative incidence of transplant-related mortality and higher probabilities of 2-year overall survival, leukemia-free survival, and GVHD-free relapse-free survival were found in the CAR-T group (P = 0.037, 0.005, 0.028 and 0.017, respectively). However, the 2-year cumulative incidence of relapse (CIR) was comparably high between two groups (26.7% in the CAR-T group and 38.3% in the NR group, P = 0.41). In the CAR-T group, patients with minimal residual disease (MRD) positive before UCBT had a high CIR comparing with those with MRD negative before UCBT (66.7% vs.19.2%, P = 0.006). Conclusion : CAR-T therapy followed by UCBT produces superior survival in R/R B-ALL, but treated patients still exhibit a high posttransplant relapse rate.

Objective: We observed the efficacy and safety of umbilical cord blood microtransplantation (UCBMT) in the treatment of newly diagnosed with acute myeloid leukemia (AML) in the elderly. Methods: Prospective one-arm phase I clinical study. The patients should meet the following criteria: 60-80-year-old; newly diagnosed AML; receive the treatment of chemotherapy combined with UCBMT. Result: In total, 11 patients newly diagnosed with AML received chemotherapy in combination with UCBMT, from November, 2019 to January, 2021, including 7 males and 4 females. The average age was 71 (60-80). For the patients, 7 cases with normal chromosome karyotype, and 2 cases with +8 chromosome, 1 case with 7q- chromosome, and 1 case with karyotype of monomer. In the 7 patients with normal chromosome karyotype, 3 cases were FMS-liketyrosine kinease 3 (FLT3) positive (2 of them in combination with nucleophosmin 1 (NPM1) mutation); in addition, in 4 patients of the 7, one showed double mutation of CEBPA, one showed NPM1 mutation, one showed IDH1 mutation, and one showed IDH2 mutation. In 4 patients with chromosomal abnormalities, one patient showed no special gene, one patient showed ASXL1 mutation, one patient was IDH1 mutation, and one patient was TP53 mutation. All of the patients were treated with IA (IDA 8-10 mg/ m 2/day x 3 days, cytarabine 100 mg/ m 2/day x 7 days) for inducing chemotherapy. For the patients with 60-70-year-old, they were treated with IDA (8 mg/ m 2/day); and for the patients with 70-80-year-old, they were treated with darubicin (10 mg/ m 2/day). In the consolidation phase, the patients were treated with cytarabine (1 g/ m 2, q12h) for 3 consecutive days. There were 3 courses of consolidation chemotherapy. Next, patients received single unrelated cord blood transplantation (UCBT) from China's public umbilical cord blood bank, HLA matching was performed for all patients before treatment. A total of 4 units of UCB with HLA 0-3/6（HLA-A,-B,-DR）matching and the ABO blood type matched with the patient were transfused after induction and consolidation chemotherapy for 24-48 hours, then with follow-up. At the same time, the immunological characteristics of these patients were fully analyzed. We demonstrated that, 8 of 11 patients received one course of induction chemotherapy, and achieved a complete response. The complete response rate was 72.7%. What's more, the median time for neutrophils ≥ 0.5 x 10 9/L and platelete ≥ 20 x 10 9/L was 12 days. There were no treatment-related deaths during induction therapy. The median follow-up was 14 (7-31) months. 1 patient showed monomer karyotype with P53 gene mutation, and got complete remission after one course of induction chemotherapy with IA. However, the patient died for AML recurred. For the other 10 patients, they were alive, and the OS of 1 year was 89.8%. Moreover, we found the expression of PD-1 on CD8 +T cells decreased, while the expression of CD38 increased after therapy. Besides, the proportion of NKp30 +NK cells, as well as the IFN-γ +TFN-α +NK cells increased significantly. Conclusion: UCBMT therapy for newly diagnosed elderly AML patients could accelerate the recovery of hematopoietic function and improve the safety of chemotherapy. This method is effective and worthy of further promotion. Disclosures No relevant conflicts of interest to declare.

Relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) has poor long-term survival even after chimeric antigen receptor (CAR)-T cell therapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several studies supported that CAR-T therapy followed by allo-HSCT is benefit for improving long-term leukemia free survival (LFS). Since probably a stronger graft versus leukemia (GVL) effect of unrelated cord blood transplantation (UCBT), it is uncertain whether consolidative UCBT is suitable for R/R B-ALL after CAR-T therapy. Here, we conducted a retrospective comparative study for R/R B-ALL patients receiving UCBT in our transplantation center. Totally 43 cases with R/R B-ALL who underwent UCBT were assigned to CAR-T group (patients achieved CR or CRi by CAR-T cell therapy before bridging to UCBT, n = 21) or non-remission (NR) group (n = 22). The median time from CAR-T infusion to UCBT was 62 (range, 42-185) days. All patients achieved neutrophil engraftment by day 42 in CAR-T group. The 180-day cumulative incidence of platelet engraftment was higher in CAR-T group than in NR group (90.5% vs 65.7%, P = 0.16). Incidence of grade II-IV and III-IV acute graft-versus-host disease (GVHD) were 28.6% and 23.8% in CAR-T group, which were both tendency lower than in NR group (45.5% and 31.8%, P = 0.32 and P = 0.63, respectively). No patient suffered from extensive chronic GVHD in CAR-T group, which was lower than in NR group (9.1%, P = 0.23). Lower 2-year cumulative incidence of transplant-related mortality (TRM), and higher probabilities of 2-year overall survival, leukemia free survival (LFS), graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) were found in CAR-T group (4.8% vs 28.2%; 75.0% vs 37.7%; 49.8% vs 23.0%; 42.4% vs 14.8%; P = 0.037, 0.005, 0.028 and 0.017; respectively). However, 2-year cumulative incidence of relapse was comparably high between CAR-T and NR group (26.7% vs 38.3%; P = 0.41). CAR-T therapy followed by UCBT has a superior survival for R/R B-ALL, but remains relatively high post-transplant relapse rate. Prevention of relapse after UCBT is warranted in this patient cohort. Disclosures No relevant conflicts of interest to declare.

BACKGROUND Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the main cause of treatment failure for patients with acute myeloid leukemia (AML). Conventional treatments such as donor lymphocyte infusions (DLI) or secondary allo-HSCT as a monotherapy or in combination with novel agents or immunotherapy showed limited improvements on long-term survival. Our previous studies have shown that a rare subset of CD4- and CD8- double negative T cells (DNTs) expanded from periphery of healthy donors are effective in targeting AML cells in vitro and in xenograft models. Also, allogeneic DNTs can be used as an off-the-shelf adoptive cellular therapy (ACT) for AML. We undertook a first in-human phase I/IIa trial to assess the safety and efficacy of escalating doses of DNTs for the treatment of AML patients relapsed post allo-HSCT. This study protocol was approved by Chinese Ethics Committee of Registering Clinical Trials. Informed consent was obtained in accordance with the Declaration of Helsinki. The trial was registered on the Chinese Clinical Trial Registry (ChiCTR-IPR-1900022795). METHODS From June 2019 to June 2020, 12 patients with relapsed AML after allo-HSCT were enrolled in the trials. Three patients received HLA-matched sibling stem cell transplant, and 9 patients received umbilical cord blood transplantation (UCBT). Hematological relapse was found in 9 cases, and molecular relapsed in 3 cases. None of the patients were able to obtain DLI from previous donors for various reasons. Clinical-grade DNTs from peripheral blood of healthy donors were expanded. After lymphodepleting chemotherapy with fludarabine and cyclophosphamide, each patient received three infusions of HLA-mismatched DNTs expanded from healthy volunteers at escalating doses of 5×107, 1×108, or 2-4×108 per kilogram of body weight at one week interval. Numbers of total DNTs and donor-derived DNTs, inflammatory cytokines levels in vivo were measured according to the study protocol. Post-remission therapy was permitted 14 days after the last DNTs infusion according to treating physician's discretion. RESULTS All surviving patients were followed until August 1st, 2020. At a median follow-up of 4.3 months (range 1.7 to 12.2 months), 1 patient withdrew from the trial after the second DNT infusion for a personal reason. 6/11 patients (54.5%) achieved complete response (CR) with 5 of these patients negative for (45.4%) minimal/measurable residual disease (MRD). 4/11 patients (36.3%) achieved partial remission. Up to the last follow-up, 4/11 patients remain CR. Increase in the levels of serum inflammatory cytokines, including interleukin (IL)-6, TNF-alpha, MCP-1, and MIP-1-beta over baseline were observed without signs of cytokine release syndrome, neurotoxicity, or graft-versus-host disease. The most common adverse events related to DNTs treatment were fever and headache. None of the patients showed >grade 2 adverse event (AE). The maximum tolerated dose was not reached. Donor DNT cell expansion was detected as early as 6 hours after infusion and reached the peak at 24 hours after the 1st infusion in most patients, slightly increased after the 2nd and 3rd infusions, and lasted for 2 weeks after 3rd infusion. However, total DNTs increased and reached the peak at 2 weeks after 3rd infusion. CONCLUSIONS Our results show that allogeneic DNTs therapy is safe, well tolerated, and potentially effective in treating AML patients who relapsed after allo-HSCT. The total number of DNTs increased after infusion. Compared to other agents, DNTs more effectively induced complete responses in this patient population. Our on-going study is to elucidate the mechanism of DNTs-mediated leukemia clearance, and explore the use of DNTs as carrier for Chimeric Antigen Receptor or transgenic TCR to further enhance the efficacy targeting resistant AML cells. Disclosures Zhang: AbbVie: Current equity holder in publicly-traded company; University Health Network: Consultancy, Current equity holder in private company, Other: Principal Investigator, Patents & Royalties.

Background Micro (mi) RNAs play an important role in the pathogenesis and development of acute myeloid leukemia (AML), and their abnormal expression may be sufficient to predict the prognosis and outcomes in AML patients. We evaluated the clinical diagnostic value of miRNA-181a-3p in predicting prognosis and outcomes in patients with AML. Methods A total of 119 newly diagnosed adult patients with AML and 60 healthy controls were recruited. Blood specimens were obtained from all AML patients at diagnosis, and 10 blood specimens were obtained on day 28 after induction chemotherapy. The controls also provided blood samples. Relative gene expression was quantified by PCR and determined using the comparative Ct method. Publicly available clinical data and gene expressions for 188 patients with AML were downloaded from TCGA data portal. Results Compared with healthy controls, the expression of miRNA-181a-3p was significantly increased in patients with AML. MiR-181a-3p expression could be used to discriminate AML patients from controls, with up-regulated expression correlating with favorable prognosis. Moreover, miRNA-181a-3p expression was significantly decreased in patients who achieved a complete response after induction chemotherapy. The multivariate Cox analysis highlighted the prognostic value of miR-181a-3p for patients with AML. Finally, we found that miR-181a-3p expression was negatively correlated with the expression of the NF-κB essential modulator (NEMO/IKBKG). Conclusions MiR-181a-3p may be clinically useful as a disease marker for AML, and enhanced the prediction of patient outcomes to chemotherapy.

Background: CD19-directed chimeric antigen receptor (CAR) T cells have substantial benefit in the treatment of patients with B-cell malignancies. However, despite encouraging therapeutic efficiency, there is limited overall response rate when anti-CD19 CAR-T cells are used to treat patients with relapsed and refractory (R/R) B cell lymphomas. Therefore, it further investigation is urgently needed to improve treatment efficacy. Method: A combined treatment protocol of CAR-T cell with decitabine (DAC) to treat B cell lymphoma was developed and tested on lymphoma cell lines first, and then efficacy and the underlying mechanism were investigated. After ethical approval was granted, the combined treatment protocol was applied to treat two patients with R/R B-cell lymphomas. Results: CAR-T cells were prepared successfully, and they recognized CD19 antigen expressed on lymphoma cell lines specifically. Cell-line studies also showed that CD19 antigen expression was increased by DAC pretreatment, and the function of CAR-T cells was not compromised. The cell-line study further demonstrated that lymphoma cells pretreated by DAC responded more to the treatment of CAR-T cells. Two patients with R/R B cell lymphoma were pretreated with DAC then treated with CAR-T, and both achieved complete remission (CR). Conclusions: The epigenetic modifying drug DAC increases expression of the surface antigen CD19 on lymphoma cells. The DAC pretreatment protocol may lead patients with B cell lymphoma to be more susceptible to adoptive transfer of anti-CD19 CAR-T cells treKeywordsatment.

For the speed and tension system of the reversible cold strip rolling mill, a dynamic surface backstepping recursive sliding mode control (DSBRSMC) strategy is proposed based on the immersion and invariance (I&I) adaptive method and the nonlinear disturbance observer (NDO). First, a relatively complete mathematical model for the speed and tension system of the reversible cold strip rolling mill driven by alternating current (AC) asynchronous motors is established. Next, the I&I adaptive method is adopted to estimate the system perturbation parameters, and the NDO is developed to observe the system uncertainty. Again, controllers for the speed and tension system are presented by combining the backstepping control, the dynamic surface control, and the recursive sliding mode control together. Theoretical analysis shows that the closed-loop system is stable in the Lyapunov sense. Finally, simulation research is conducted by using the actual data, and results show the validity of the proposed control strategy.

The arsenic species in rat plasma were studied after oral administration of realgar and Niu Huang Jie Du Pian (NHJDP) and the possible compatible effects of realgar was evaluated by comparing the pharmacokinetics of arsenic species after administration of realgar and NHJDP. The separation of the arsenicals was performed by a high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS) technique. Dimethylarsinic acid (DMA) was found to be the main species in rats’ plasma after dosing. No traces of arsenite [As(Ⅲ)], monomethylarsonic acid (MMA) or arsenate [As(Ⅴ)] were detected at any sampling time points. Compared with realgar administration alone, dose-normalized peak concentration(C(max)) and AUC(0-t) of DMA were significantly decreased by NHJDP administration, while the t(max) was significantly delayed with the clearance and apparent volume of distribution significantly increased, indicating that the pharmacokinetics of As from realgar was affected by other ingredients in the compound prescription of NHJDP.

Acute promyelocytic leukemia (APL) is typically characterized by the chromosomal rearrangement, t(15;17)(q22;q12), which has breakpoints in the PML and RARA (also known as RARa) genes leading to ge...

Ethanol has great potential to be a candidate for the source of light olefins such as ethylene and propylene. However, ethanol to olefin (ETO) process has not been fully investigated. In this work, the conversion reactions of ethanol were carried out at 673 K under atmospheric pressure on SAPO-34 and SAPO-34/SiO2 catalysts. SAPO-34 and SAPO-34/SiO2 exhibit higher selectivity for propylene than H-ZSM-5 zeolite catalysts do. The SAPO-34 with silica binder showed better catalytic performance for the transformation of ethanol to propylene than the SAPO-34 catalyst.