Publications by authors named "Xiang Wan"

158 Publications

Ligand assisted hydride transfer: a pivotal step for CO₂ hydroboration catalyzed by a mononuclear Mn(I) PNP complex.

Chem Asian J 2021 Jul 18. Epub 2021 Jul 18.

Huazhong University of Science and Technology, School of Chemistry and Chemical Engineering, CHINA.

A mononuclear Mn(I) pincer complex [Mn(Ph₂PCH₂SiMe₂)₂NH(CO)₂Br] was disclosed to catalyze the pinacolborane (HBpin)-based CO₂ hydroboration reaction. Density functional calculations were conducted to reveal the reaction mechanism. The calculations showed that the reaction mechanism could be divided into four stages: (1) the addition of HBpin to the unsaturated catalyst C1; (2) the reduction of CO₂ to HCOOBpin; (3) the reduction of HCOOBpin to HCHO; (4) the reduction of HCHO to CH₃OBpin. The activation of HBpin is the ligand-assisted addition of HBpin to the unsaturated Mn(I)-N complex C1 generated by the elimination of HBr from the Mn(I) pincer catalyst. The sequential substrate reductions share a common mechanism, and every hydroboration commences with the nucleophilic attack of the Mn(I)-H to the electron-deficient carbon centers. The hydride transfer from Mn(I) to HCOOBpin was found to be the rate-limiting step for the whole catalytic reaction, with a total barrier of 27.0 kcal/mol, which fits well with the experimental observations at 90 ºC. The reactivity trend of CO₂, HCOOBpin, HCHO, and CH₃OBpin was analyzed through both thermodynamic and kinetic analysis, in the following order, namely HCHO > CO₂ > HCOOBpin >> CH₃OBpin. Importantly, the very high barrier for the reduction of CH₃OBpin to form CH₄ reconciles with the fact that methane was not observed in this catalytic reaction.
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http://dx.doi.org/10.1002/asia.202100582DOI Listing
July 2021

Acute and chronic toxicity of microcystin-LR and phenanthrene alone or in combination to the cladoceran (Daphnia magna).

Ecotoxicol Environ Saf 2021 Sep 12;220:112405. Epub 2021 Jun 12.

State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, 73 East Beijing Road, Nanjing 210008, China. Electronic address:

Hazardous substances, such as microcystin-LR (MC-LR) and phenanthrene (Phe) are ubiquitous co-contaminants in eutrophic freshwaters, which cause harms to aquatic organisms. However, the risks associated with the co-exposure of aquatic biota to these two chemicals in the environment have received little attention. In this study, the single and mixture toxic effects of MC-LR and Phe mixtures were investigated in Daphnia magna after acute and chronic exposure. Acute tests showed that the median effective concentrations (48 h) for MC-LR, Phe and their mixtures were 13.46, 0.57 and 8.84 mg/L, respectively. Mixture toxicity prediction results indicated that the independent action model was more applicable than the concentration addition model. Moreover, combination index method suggested that the mixture toxicity was concentration dependent. Synergism was elicited at low concentrations of MC-LR and Phe exposure (≤4.04 + 0.17 mg/L), whereas antagonistic or additive effects were induced at higher concentrations. The involved mechanism of antagonism was presumably attributable to the protective effects of detoxification genes activated by high concentrations of MC-LR in mixtures. Additionally, chronic results also showed that exposure to a MC-LR and Phe mixture at low concentrations (≤50 +2 μg/L) resulted in greater toxic effects on D. magna life history than either chemical acting alone. The significant inhibition on detoxification genes and increased accumulation of MC-LR could be accounted for their synergistic toxic effects on D. magna. Our findings revealed the exacerbated ecological hazard of MC-LR and Phe at environmental concentrations (≤50 +2 μg/L), and provided new insights to the potential toxic mechanisms of MC-LR and Phe in aquatic animals.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112405DOI Listing
September 2021

Incidence and risk factors of late-onset hemorrhagic cystitis after single umbilical cord blood transplantation with myeloablative conditioning regimen.

Int J Hematol 2021 Jun 12. Epub 2021 Jun 12.

Department of Hematology of Anhui Provincial Hospital, Anhui Medical University, Hefei, China.

Objective: To explore the incidence and risk factors of late-onset hemorrhagic cystitis (LOHC) in patients undergoing single umbilical cord blood transplantation for hematological malignancies.

Methods: Clinical data from 234 patients who consecutively underwent single UCBT using a myeloablative conditioning regimen without antithymocyte globulin in our center were retrospectively analyzed.

Results: In total, 64 (27.4%) patients developed LOHC with a median onset time of 40.5 (range 8-154) days, and 15 (6.4%) patients gradually developed grade III-IV LOHC. The incidence of LOHC was marginally higher in adults (31.0%) than in children (23.7%) (p = 0.248). HLA matching ≤ 6/8 (HR = 2.624, 95% CI 1.112-6.191, p = 0.028) was an independent risk factor for LOHC. The overall survival of LOHC patients (59.8%, 95% CI 61.7-85.5%) was significantly lower than that of patients without LOHC (86.8%, 95% CI 79.6-91.6%) at 130 days post transplantation (p = 0.036).

Conclusion: Patients with less well-matched grafts have a higher incidence of LOHC. Inherent deficiencies in immunity in the context of HLA disparity and more intense pharmacologic immunosuppression after severe acute graft-versus-host disease may contribute to viral activation. Prevention and treatment of LOHC have the potential to prolong long-term survival.
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http://dx.doi.org/10.1007/s12185-021-03168-wDOI Listing
June 2021

TSCCA: A tensor sparse CCA method for detecting microRNA-gene patterns from multiple cancers.

PLoS Comput Biol 2021 Jun 1;17(6):e1009044. Epub 2021 Jun 1.

Shenzhen Research Institute of Big Data, Shenzhen, China.

Existing studies have demonstrated that dysregulation of microRNAs (miRNAs or miRs) is involved in the initiation and progression of cancer. Many efforts have been devoted to identify microRNAs as potential biomarkers for cancer diagnosis, prognosis and therapeutic targets. With the rapid development of miRNA sequencing technology, a vast amount of miRNA expression data for multiple cancers has been collected. These invaluable data repositories provide new paradigms to explore the relationship between miRNAs and cancer. Thus, there is an urgent need to explore the complex cancer-related miRNA-gene patterns by integrating multi-omics data in a pan-cancer paradigm. In this study, we present a tensor sparse canonical correlation analysis (TSCCA) method for identifying cancer-related miRNA-gene modules across multiple cancers. TSCCA is able to overcome the drawbacks of existing solutions and capture both the cancer-shared and specific miRNA-gene co-expressed modules with better biological interpretations. We comprehensively evaluate the performance of TSCCA using a set of simulated data and matched miRNA/gene expression data across 33 cancer types from the TCGA database. We uncover several dysfunctional miRNA-gene modules with important biological functions and statistical significance. These modules can advance our understanding of miRNA regulatory mechanisms of cancer and provide insights into miRNA-based treatments for cancer.
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http://dx.doi.org/10.1371/journal.pcbi.1009044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195367PMC
June 2021

Clinical decision-making framework against over-testing based on modeling implicit evaluation criteria.

J Biomed Inform 2021 Jul 24;119:103823. Epub 2021 May 24.

Unisound AI Technology Co., Ltd, Beijing 100083, China.

Different statistical methods include various subjective criteria that can prevent over-testing. However, no unified framework that defines generalized objective criteria for various diseases is available to determine the appropriateness of diagnostic tests recommended by doctors. We present the clinical decision-making framework against over-testing based on modeling the implicit evaluation criteria (CDFO-MIEC). The CDFO-MIEC quantifies the subjective evaluation process using statistics-based methods to identify over-testing. Furthermore, it determines the test's appropriateness with extracted entities obtained via named entity recognition and entity alignment. More specifically, implicit evaluation criteria are defined-namely, the correlation among the diagnostic tests, symptoms, and diseases, confirmation function, and exclusion function. Additionally, four evaluation strategies are implemented by applying statistical methods, including the multi-label k-nearest neighbor and the conditional probability algorithms, to model the implicit evaluation criteria. Finally, they are combined into a classification and regression tree to make the final decision. The CDFO-MIEC also provides interpretability by decision conditions for supporting each clinical decision of over-testing. We tested the CDFO-MIEC on 2,860 clinical texts obtained from a single respiratory medicine department in China with the appropriate confirmation by physicians. The dataset was supplemented with random inappropriate tests. The proposed framework excelled against the best competing text classification methods with a Mean_F of 0.9167. This determined whether the appropriate and inappropriate tests were properly classified. The four evaluation strategies captured the features effectively, and they were imperative. Therefore, the proposed CDFO-MIEC is feasible because it exhibits high performance and can prevent over-testing.
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http://dx.doi.org/10.1016/j.jbi.2021.103823DOI Listing
July 2021

The use of different sublethal endpoints to monitor atrazine toxicity in nematode Caenorhabditis elegans.

Chemosphere 2021 Jul 3;274:129845. Epub 2021 Feb 3.

Nanjing Institute of Environmental Science, Ministry of Ecology and Environment, Nanjing, 210042, China. Electronic address:

In this work, Caenorhabditis elegans was employed as an in vivo model to determine the toxic effects of atrazine at different concentrations. After the exposure period from the larval stage L1 to adulthood day 1, atrazine (10 mg/L) significantly decreased the body length and lifespan of nematodes. In addition, exposure to ≥0.01 mg/L atrazine remarkably increased the intestinal reactive oxygen species (ROS) levels and reduced locomotion behavior of nematodes, while exposure to ≥ 1 mg/L atrazine decreased the brood size of nematodes. Moreover, atrazine (0.001-0.1 mg/L) upregulated the expression levels of hsp-6::GFP and hsp-6/60 in nematodes, indicating the activation of mitochondrial unfolded protein response (mtUPR). On the contrary, atrazine (1-10 mg/L) downregulated the expression levels of hsp-6::GFP and hsp-6/60 in nematodes. Furthermore, mtUPR induction governed by the RNAi knockdown of atfs-1 could increase the vulnerability of nematodes against atrazine toxicity. Overall, our findings highlighted the dynamic responses of nematodes toward different concentrations of atrazine, which could be monitored using different sublethal endpoints as bioindicators.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129845DOI Listing
July 2021

CD19-targeted chimeric antigen receptor-modified T cells induce remission in patients with relapsed acute B lymphoblastic leukemia after umbilical cord blood transplantation.

Chin Med J (Engl) 2021 May 6. Epub 2021 May 6.

Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui 230031, China Department of Hematology, The First Affiliated Hospital of USCT, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China PersonGen-Anke Cellular Therapeutics Co., Ltd., Hefei, Anhui 230001, China.

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http://dx.doi.org/10.1097/CM9.0000000000001491DOI Listing
May 2021

Valproic Acid-Induced Changes of 4D Nuclear Morphology in Astrocyte Cells.

Mol Biol Cell 2021 Apr 28:mbcE20080502. Epub 2021 Apr 28.

Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.

Histone deacetylase inhibitors, such as valproic acid (VPA), have important clinical therapeutic and cellular reprogramming applications. They induce chromatin re-organization that is associated with altered cellular morphology. However, there is a lack of comprehensive characterization of VPA-induced changes of nuclear size and shape. Here, we quantify 3D nuclear morphology of primary human astrocyte cells treated with VPA over time (hence, 4D). We compared volumetric and surface-based representations and identified seven features that jointly discriminate between normal and treated cells with 85% accuracy on day 7. From day 3, treated nuclei were more elongated and flattened and then continued to morphologically diverge from controls over time, becoming larger and more irregular. On day 7, most of the size and shape descriptors demonstrated significant differences between treated and untreated cells, including a 24% increase in volume and 6% reduction in extent (shape regularity) for treated nuclei. Overall, we show that 4D morphometry can capture how chromatin re-organization modulates the size and shape of the nucleus over time. These nuclear structural alterations may serve as a biomarker for histone (de-)acetylation events and provide insights into mechanisms of astrocytes-to-neurons reprogramming.
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http://dx.doi.org/10.1091/mbc.E20-08-0502DOI Listing
April 2021

Outcomes of Adolescents and Young Adults Compared with Children with Acute Leukemia after Single-Unit Unrelated Cord Blood Transplantation Using Myeloablative Conditioning without Antithymocyte Globulin.

Acta Haematol 2021 Apr 13:1-11. Epub 2021 Apr 13.

Department of Hematology, Anhui Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Background: Although the use of cord blood transplantation (CBT) is becoming more frequent in acute leukemia, considering the relationship between the low stem cell dose and graft failure, whether use of CBT for adolescents and young adults (AYAs) is appropriate remains uncertain.

Methods: A retrospective registry-based analysis of clinical outcomes and immune reconstitution was conducted for 105 AYAs and 187 children with acute leukemia who underwent single-unit CBT using myeloablative conditioning (MAC) without antithymocyte globulin (ATG).

Results: Outcomes were similar between AYAs and children, except for nonrelapse mortality (NRM) and recovery rates of neutrophils and platelets. The 30-day cumulative incidence of neutrophil engraftment was similar between AYAs and children, but children had faster rates of neutrophil and platelet recovery than AYAs. The median time to neutrophil engraftment was earlier in children than in AYAs (AYAs, 19 days, 95% confidence interval [CI] 17.3-21.7; children, 16 days, 95% CI 13.1-19.5, p = 0.00003). The incidence of platelet recovery on day 120 was higher in children than in AYAs (AYAs, 80%, 95% CI 71-81%; children, 88%, 95% CI 82-92%, p = 0.037). CD34+ cell dose was the only independent factor influencing both neutrophil and platelet recovery. The cumulative incidence of NRM at 2 years was higher among AYAs than among children (AYAs, 27.5%, 95% CI 20-37%; children, 15%, 95% CI 10-21%, p = 0.008). Conditioning regimen was an independent factor influencing NRM. With respect to immune reconstitution, natural killer cell counts quickly recovered to normal levels 1-month post-CBT in both children and AYAs. CD8+ T-cell counts were higher in children than in AYAs at 1 and 3 months post-CBT. CD4+ T-cell counts were similar in both children and AYAs after CBT.

Conclusion: AYAs with acute leukemia have outcomes of single-unit CBT using MAC without ATG that are as good as those of children. Thus, single-unit CBT using modified MAC without ATG is an acceptable choice for both AYAs and children who do not have a suitable donor.
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http://dx.doi.org/10.1159/000507973DOI Listing
April 2021

A unified framework for cross-population trait prediction by leveraging the genetic correlation of polygenic traits.

Am J Hum Genet 2021 04 25;108(4):632-655. Epub 2021 Mar 25.

Guangzhou HKUST Fok Ying Tung Research Institute, Guangzhou 511458, China; Department of Mathematics, The Hong Kong University of Science and Technology, Hong Kong SAR, China. Electronic address:

The development of polygenic risk scores (PRSs) has proved useful to stratify the general European population into different risk groups. However, PRSs are less accurate in non-European populations due to genetic differences across different populations. To improve the prediction accuracy in non-European populations, we propose a cross-population analysis framework for PRS construction with both individual-level (XPA) and summary-level (XPASS) GWAS data. By leveraging trans-ancestry genetic correlation, our methods can borrow information from the Biobank-scale European population data to improve risk prediction in the non-European populations. Our framework can also incorporate population-specific effects to further improve construction of PRS. With innovations in data structure and algorithm design, our methods provide a substantial saving in computational time and memory usage. Through comprehensive simulation studies, we show that our framework provides accurate, efficient, and robust PRS construction across a range of genetic architectures. In a Chinese cohort, our methods achieved 7.3%-198.0% accuracy gain for height and 19.5%-313.3% accuracy gain for body mass index (BMI) in terms of predictive R compared to existing PRS approaches. We also show that XPA and XPASS can achieve substantial improvement for construction of height PRSs in the African population, suggesting the generality of our framework across global populations.
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http://dx.doi.org/10.1016/j.ajhg.2021.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059341PMC
April 2021

IDO1 as a new immune biomarker for diabetic nephropathy and its correlation with immune cell infiltration.

Int Immunopharmacol 2021 May 10;94:107446. Epub 2021 Feb 10.

Department of Nephrology, Qilu Hospital of Shandong University, Jinan, 250012 Shandong, China. Electronic address:

Introduction: Indoleamine 2,3-dioxygenase 1(IDO1) has complicated roles in immune-inflammatory response regulation, but its correlation with immune cell infiltration in diabetic nephropathy (DN) remains unknown.

Methods: Gene expression data were extracted from the GEO database. Differentially expressed genes (DEGs) were identified and functional correlation analysis was performed. The immune hub gene was screened using Maximal Clique Centrality, and verified in DN model mice via western blotting, immunohistochemistry, and immunofluorescence analysis. CIBERSORTx was used to assign values to immune cell infiltration in DN and determine a correlation with the hub gene. The prognostic significance of the hub gene was then validated.

Results: The 330 screened DEGs from the GEO dataset were most enriched in GO functions and KEGG pathways associated with immune inflammation. IDO1 was identified as a hub immune gene, with upregulated expression in DN model mice. IDO1 expression was positively correlated with M1 macrophages (R = 0.58, P < 0.001) and monocytes (R = 0.44, P = 0.049), and was negatively correlated with resting memory CD4 T cells (R = -0.51, P = 0.019). IDO1 expression was upregulated in peritoneal macrophages after high glucose stimulation, and inflammatory factor production was reversed by IDO1 inhibition. Higher IDO1 expression was associated with worse prognosis in DN patients via multivariate survival analysis (P < 0.001).

Conclusions: IDO1 was identified as a diagnostic and prognostic biomarker for DN and shown to play a vital role in immune cell infiltration in DN, ascertained using microarray data and CIBERSORTx for the first time.
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http://dx.doi.org/10.1016/j.intimp.2021.107446DOI Listing
May 2021

A Novel Sparse Graph-Regularized Singular Value Decomposition Model and Its Application to Genomic Data Analysis.

IEEE Trans Neural Netw Learn Syst 2021 Feb 8;PP. Epub 2021 Feb 8.

Learning the gene coexpression pattern is a central challenge for high-dimensional gene expression analysis. Recently, sparse singular value decomposition (SVD) has been used to achieve this goal. However, this model ignores the structural information between variables (e.g., a gene network). The typical graph-regularized penalty can be used to incorporate such prior graph information to achieve more accurate discovery and better interpretability. However, the existing approach fails to consider the opposite effect of variables with negative correlations. In this article, we propose a novel sparse graph-regularized SVD model with absolute operator (AGSVD) for high-dimensional gene expression pattern discovery. The key of AGSVD is to impose a novel graph-regularized penalty (|u|TL|u|). However, such a penalty is a nonconvex and nonsmooth function, so it brings new challenges to model solving. We show that the nonconvex problem can be efficiently handled in a convex fashion by adopting an alternating optimization strategy. The simulation results on synthetic data show that our method is more effective than the existing SVD-based ones. In addition, the results on several real gene expression data sets show that the proposed methods can discover more biologically interpretable expression patterns by incorporating the prior gene network.
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http://dx.doi.org/10.1109/TNNLS.2021.3054635DOI Listing
February 2021

Donor KIR3DL1/receptor HLA-Bw4-80I Combination Reduces Acute Leukemia Relapse after Umbilical Cord Blood Transplantation without in Vitro T-cell Depletion.

Mediterr J Hematol Infect Dis 2021 1;13(1):e2021005. Epub 2021 Jan 1.

Department of Hematology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui, 230001, China.

Background: Donor natural killer (NK) cell alloreactivity in umbilical cord bone marrow transplantation (UCBT) can lead to leukemic relapse. However, NK cell function is calibrated by interaction with human leukocyte antigens (HLAs). This study aimed to investigate graft-resistant leukemia after transplantation and compared specific genotypes of killer immunoglobulin-like receptors (KIRs) in donors and human leukocyte antigen ligands in patients.

Methods: We retrospectively analyzed 232 patients with acute leukemia from a single center. Patients had undergone UCBT with myeloablative conditioning and without anti-thymocyte globulin. We identified the KIR genotypes of cord blood donors using polymerase chain reaction with sequence-specific primers. All of the donors contained KIR3DL1.

Results: The patients were divided into three groups according to the HLA-B locus. The donor KIR3DL1 and recipient HLA-Bw4-80I combination was predictive of being highly educated and was associated with a lower relapse (=0.006) and better overall survival (probability of relapse=0.13, < 0.001) than the uneducated group. We found no significant increase in the incidence of acute or chronic graft-versus-host disease.

Conclusions: Our data suggest that the donor KIR3DL1/receptor and HLA-Bw4-80I combination in UCBT results in stronger graft-versus-leukemia effects and improved outcomes in patients with acute leukemia.
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http://dx.doi.org/10.4084/MJHID.2021.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813285PMC
January 2021

Umbilical cord blood transplantation can overcome the poor prognosis of KMT2A-MLLT3 acute myeloid leukemia and can lead to good GVHD-free/relapse-free survival.

Ann Hematol 2021 May 20;100(5):1303-1309. Epub 2021 Jan 20.

Department of Hematology of Anhui Provincial Hospital, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, No. 17 Lujiang Road, Hefei, Anhui, 230001, People's Republic of China.

This is a retrospective study comparing the effectiveness of umbilical cord blood transplantation (UCBT) and chemotherapy for patients in the first complete remission period for acute myeloid leukemia with KMT2A-MLLT3 rearrangements. A total of 22 patients were included, all of whom achieved first complete remission (CR1) through 1-2 rounds of induction chemotherapy, excluding patients with an early relapse. Twelve patients were treated with UCBT, and 10 patients were treated with chemotherapy after 2 to 4 courses of consolidation therapy. The 3-year overall survival (OS) of the UCBT group was 71.3% (95% CI, 34.4-89.8%), and that of the chemotherapy group was 10% (95% CI, 5.89-37.3%). The OS of the UCBT group was significantly higher than that of the chemotherapy group (P = 0.003). The disease-free survival (DFS) of the UCBT group was 60.8% (95% CI, 25.0-83.6%), which was significantly higher than the 10% (95% CI, 5.72-35.8%) of the chemotherapy group (P = 0.003). The relapse rate of the UCBT group was 23.6% (95% CI, 0-46.8%), and that of the chemotherapy group was 85.4% (95% CI, 35.8-98.4%), which was significantly higher than that of the UCBT group (P < 0.001). The non-relapse mortality (NRM) rate in the UCBT group was 19.8% (95% CI, 0-41.3%), and that in the chemotherapy group was 0.0%. The NRM rate in the UCBT group was higher than that in the chemotherapy group, but there was no significant difference between the two groups (P = 0.272). Two patients in the UCBT group relapsed, two died of acute and chronic GVHD, and one patient developed chronic GVHD 140 days after UCBT and is still alive, so the GVHD-free/relapse-free survival (GRFS) was 50% (95% CI, 17.2-76.1%). AML patients with KMT2A-MLLT3 rearrangements who receive chemotherapy as their consolidation therapy after CR1 have a very poor prognosis. UCBT can overcome the poor prognosis and significantly improve survival, and the GRFS for these patients is very good. We suggest that UCBT is a better choice than chemotherapy for KMT2A-MLLT3 patients.
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http://dx.doi.org/10.1007/s00277-021-04413-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043860PMC
May 2021

Hypoxia-preconditioned adipose-derived stem cells combined with scaffold promote urethral reconstruction by upregulation of angiogenesis and glycolysis.

Stem Cell Res Ther 2020 12 11;11(1):535. Epub 2020 Dec 11.

Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No.639, Zhizaoju Road in Huangpu District, Shanghai, 200011, China.

Rationale: Tissue engineering is a promising alternative for urethral reconstruction, and adipose-derived stem cells (ADSCs) are widely used as seeding cells. Hypoxia preconditioning can significantly enhance the therapeutic effects of ADSCs. The low oxygen tension of postoperative wound healing is inevitable and may facilitate the nutritional function of ADSCs. This study aimed to investigate if hypoxia-preconditioned ADSCs, compared to normoxia-preconditioned ADSCs, combined with scaffold could better promote urethral reconstruction and exploring the underlying mechanism.

Methods: In vitro, paracrine cytokines and secretomes that were secreted by hypoxia- or normoxia-preconditioned ADSCs were added to cultures of human umbilical vein endothelial cells (HUVECs) to measure their functions. In vivo, hypoxia- or normoxia-preconditioned ADSCs were seeded on a porous nanofibrous scaffold for urethral repair on a defect model in rabbits.

Results: The in vitro results showed that hypoxia could enhance the secretion of VEGFA by ADSCs, and hypoxia-preconditioned ADSCs could enhance the viability, proliferation, migration, angiogenesis, and glycolysis of HUVECs (p < 0.05). After silencing VEGFA, angiogenesis and glycolysis were significantly inhibited (p < 0.05). The in vivo results showed that compared to normoxia-preconditioned ADSCs, hypoxia-preconditioned ADSCs combined with scaffolds led to a larger urethral lumen diameter, preserved urethral morphology, and enhanced angiogenesis (p < 0.05).

Conclusions: Hypoxia preconditioning of ADSCs combined with scaffold could better promote urethral reconstruction by upregulating angiogenesis and glycolysis. Hypoxia-preconditioned ADSCs combined with novel scaffold may provide a promising alternative treatment for urethral reconstruction.
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http://dx.doi.org/10.1186/s13287-020-02052-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731784PMC
December 2020

PRC1 is a critical regulator for anaphase spindle midzone assembly and cytokinesis in mouse oocyte meiosis.

FEBS J 2021 05 30;288(9):3055-3067. Epub 2020 Nov 30.

College of Animal Science and Technology, Nanjing Agricultural University, China.

Protein regulator of cytokinesis 1 (PRC1) is a microtubule bundling protein that is involved in the regulation of the central spindle bundle and spindle orientation during mitosis. However, the functions of PRC1 during meiosis have rarely been studied. In this study, we explored the roles of PRC1 during meiosis using an oocyte model. Our results found that PRC1 was expressed at all stages of mouse oocyte meiosis, and PRC1 accumulated in the midzone/midbody during anaphase/telophase I. Moreover, depleting PRC1 caused defects in polar body extrusion during mouse oocyte maturation. Further analysis found that PRC1 knockdown did not affect meiotic spindle formation or chromosome segregation; however, deleting PRC1 prevented formation of the midzone and midbody at the anaphase/telophase stage of meiosis I, which caused cytokinesis defects and further induced the formation of two spindles in the oocytes. PRC1 knockdown increased the level of tubulin acetylation, indicating that microtubule stability was affected. Furthermore, KIF4A and PRC1 showed similar localization in the midzone/midbody of oocytes at anaphase/telophase I, while the depletion of KIF4A affected the expression and localization of PRC1. The PRC1 mRNA injection rescued the defects caused by PRC1 knockdown in oocytes. In summary, our results suggest that PRC1 is critical for midzone/midbody formation and cytokinesis under regulation of KIF4A in mouse oocytes.
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http://dx.doi.org/10.1111/febs.15634DOI Listing
May 2021

Decitabine prior to salvaged cord blood transplantation for acute myeloid leukaemia/myelodysplastic syndrome not in remission.

J Clin Pharm Ther 2020 Dec 3;45(6):1372-1381. Epub 2020 Oct 3.

Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Sciences and Technology of China, Hefei, Anhui, P. R. China.

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.
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http://dx.doi.org/10.1111/jcpt.13231DOI Listing
December 2020

Recombinant human thrombopoietin promotes platelet engraftment after umbilical cord blood transplantation.

Blood Adv 2020 08;4(16):3829-3839

Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT) accompanied by increased transplant-related complications or death. This study was designed to determine the safety and efficacy of recombinant human thrombopoietin (rhTPO) in promoting platelet engraftment after UCBT. A total of 120 patients scheduled to receive UCBT were randomly assigned to the rhTPO group (300 U/kg once daily from days 14 to 28 after UCBT, n = 60) or the control group (n = 60). The primary outcome was the 60-day cumulative incidence of platelet engraftment after single-unit cord blood transplantation. The 60-day cumulative incidence of platelet engraftment (platelet count ≥20 × 109/L) and the 120-day cumulative incidence of platelet recovery (platelet count ≥50 × 109/L) were both significantly higher in the rhTPO group than in the control group (83.1% vs 66.7%, P = .020; and 81.4% vs 65.0%, P = .032, respectively). In addition, the number of required platelet infusions was significantly lower in the rhTPO group than in the control group (6 vs 8 units, respectively; P = .026). The cumulative incidence of neutrophil engraftment and the probability of 2-year overall survival, disease-free survival, and graft-versus-host disease-free relapse-free survival did not differ between the 2 groups. Other transplant-related outcomes and complications did not differ between the 2 groups, and no severe adverse effects were observed in patients receiving rhTPO. This study demonstrated that rhTPO is well tolerated in patients and could effectively promote platelet engraftment after UCBT. This study was registered on the Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx) as ChiCTR-IPR-16009357.
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http://dx.doi.org/10.1182/bloodadvances.2020002257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448600PMC
August 2020

Occurrence and risk assessment of microcystin and its relationship with environmental factors in lakes of the eastern plain ecoregion, China.

Environ Sci Pollut Res Int 2020 Dec 10;27(36):45095-45107. Epub 2020 Aug 10.

State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, 73 East Beijing Road, Nanjing, 210008, China.

The frequent occurrence of microcystins (MCs) in freshwater poses serious threats to the drinking water safety and health of human beings. Although MCs have been detected in individual fresh waters in China, little is known about their occurrence over a large geographic scale. An investigation of 30 subtropical lakes in eastern China was performed during summer 2018 to determine the MCs concentrations in water and their possible risk via direct water consumption to humans, and to assess the associated environmental factors. MCs were detected in 28 of 30 lakes, and the highest mean MCs concentrations occurred in Lake Chaohu (26.7 μg/L), followed by Lake Taihu (3.11 μg/L). MC-LR was the primary variant observed in our study, and MCs were mainly produced by Microcystis, Anabaena (Dolicospermum), and Oscillatoria in these lakes. Replete nitrogen and phosphorus concentrations, irradiance, and stable water column conditions were critical for dominance of MC-producing cyanobacteria and high MCs production in our study. Hazard quotients indicated that human health risk of MCs in most lakes was at moderate or low levels except Lakes Chaohu and Taihu. Nutrient control management is recommended to decrease the likelihood of high MCs production. Finally, we recommend the regional scale thresholds of total nitrogen and total phosphorus concentrations of 1.19 mg/L and 7.14 × 10 mg/L, respectively, based on the drinking water guideline of MC-LR (1 μg/L) recommended by World Health Organization. These targets for nutrient control will aid water quality managers to reduce human health risks created by exposure to MCs.
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http://dx.doi.org/10.1007/s11356-020-10384-0DOI Listing
December 2020

Information Metamaterial Systems.

iScience 2020 Aug 23;23(8):101403. Epub 2020 Jul 23.

State Key Laboratory of Millimeter Waves, Southeast University, Nanjing 210096, China.

Metamaterials have great capabilities and flexibilities in controlling electromagnetic (EM) waves because their subwavelength meta-atoms can be designed and tailored in desired ways. However, once the structure-only metamaterials (i.e., passive metamaterials) are fabricated, their functions will be fixed. To control the EM waves dynamically, active devices are integrated into the meta-atoms, yielding active metamaterials. Traditionally, the active metamaterials include tunable metamaterials and reconfigurable metamaterials, which have either small-range tunability or a few numbers of reconfigurability. Recently, a special kind of active metamaterials, digital coding and programmable metamaterials, have been presented, which can realize a large number of distinct functionalities and switch them in real time with the aid of field programmable gate array (FPGA). More importantly, the digital coding representations of metamaterials make it possible to bridge the digital world and physical world using the metamaterial platform and make the metamaterials process digital information directly, resulting in information metamaterials. In this review article, we firstly introduce the evolution of metamaterials and then present the concepts and basic principles of digital coding metamaterials and information metamaterials. With more details, we discuss a series of information metamaterial systems, including the programmable metamaterial systems, software metamaterial systems, intelligent metamaterial systems, and space-time-coding metamaterial systems. Finally, we introduce the current progress and predict the future trends of information metamaterials.
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http://dx.doi.org/10.1016/j.isci.2020.101403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415848PMC
August 2020

An extracellular matrix-mimicking, bilayered, heterogeneous, porous, nanofibrous scaffold for anterior urethroplasty in a rabbit model.

Biomed Mater 2020 09 24;15(6):065008. Epub 2020 Sep 24.

Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, People's Republic of China. These authors have contributed equally.

Anterior urethral reconstruction is still a challenging clinical task, and tissue engineering technology offers new options for anterior urethroplasty. In this work, we evaluated an extracellular matrix (ECM) mimicking scaffold for anterior urethral reconstruction in a New Zealand white rabbit model. After the creation of a urethral defect, the ECM-mimicking scaffold was applied in six rabbits, and small intestinal submucosa (SIS) was used in three rabbits. The outcomes of urethrography and histological analysis were evaluated six months postoperatively. A larger urethral diameter was observed in the ECM-mimicking scaffolds (3.01 ± 0.12 mm) than in the SIS grafts (0.95 ± 0.07 mm). Urethral fistulae and stenosis were observed in the SIS grafts. Urothelial and smooth muscle cells were observed in all rabbits, but the ECM-mimicking scaffold showed better performance. The ECM-mimicking scaffold may be an effective clinical treatment option for congenital and acquired urethral pathologies.
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http://dx.doi.org/10.1088/1748-605X/ab9fd0DOI Listing
September 2020

Lowly expressed lncRNA PVT1 suppresses proliferation and advances apoptosis of glioma cells through up-regulating microRNA-128-1-5p and inhibiting PTBP1.

Brain Res Bull 2020 10 17;163:1-13. Epub 2020 Jun 17.

Department of Neurosurgery, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Foshan, 528300, Guangdong, China. Electronic address:

Background: Glioma is a primary intracranial malignancy with poor prognosis, of which the pathogenesis remains to be elucidated. Therein, the aim of this study is to discuss the impacts of lncRNA plasmacytoma variant translocation 1 (PVT1)/microRNA-128-1-5p (miR-128-1-5p)/polypyrimidine tract-binding protein 1 (PTBP1) axis on the biological characteristics of glioma cells.

Methods: Glioma tissue samples (72 cases) and normal brain tissue samples (35 cases) were harvested. The expression of PVT1, miR-128-1-5p and PTBP1 in glioma tissues and cells was detected. Glioma cells were transfected with sh-PVT1, miR-128-1-5p mimics or miR-128-1-5p inhibitors to verify the impacts of PVT1 and miR-128-1-5p on DNA damage, cell colony formation, invasion, proliferation, migration and apoptosis of glioma U87 and U251 cells. The growth of transplanted tumor was tested by tumor xenograft in nude mice. The combination of PVT1 and miR-128-1-5p and the targeting relationship between miR-128-1-5p and PTBP1 were verified.

Results: PVT1 and PTBP1 expression was enhanced and miR-128-1-5p expression was degraded in glioma tissues and cells. Overexpressed miR-128-1-5p and lowly-expressed PVT1 promoted DNA damage, suppressed colony formation, invasion, proliferation and migration as well as boosted apoptosis of U251 and U87 cells. Up-regulating miR-128-1-5p and down-regulating PVT1 reduced transplanted tumor volume and weight of glioma in mice. Low expression miR-128-1-5p reversed the effect of low expression PVT1 on the biological characteristics of glioma cells. PVT1 specifically bound to miR-128-1-5p and PTBP1 was the target gene of miR-128-1-5p.

Conclusion: This study suggests that down-regulated PVT1 or up-regulated miR-128-1-5p boosts apoptosis and attenuates proliferation of glioma cells by inhibiting PTBP1 expression. This study is essential for finding new therapeutic targets for glioma.
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http://dx.doi.org/10.1016/j.brainresbull.2020.06.006DOI Listing
October 2020

[comIdiopathic scrotal calcinosis: A report of 10 cases and review of the literature].

Zhonghua Nan Ke Xue 2019 Jun;25(6):544-548

Department of Urology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.

Objective: To investigate the clinical features, pathogenesis, diagnosis and scrotal reconstruction in the treatment of idiopathic scrotal calcinosis (ISC).

Methods: From March 2007 to October 2018, 10 ISC patients, aged 28-79 (mean 45) years and with a disease course of 6-497 (mean 128.4) months, were treated in our hospital. We retrospectively analyzed their clinical data and reviewed related literature.

Results: All the patients underwent physical examination and biochemical and parathyroid function tests. None of them had a history of endocrine or metabolic disease, or trauma, or a family member with similar diseases, and none had subjective symptoms except local pruritus in 1 case. All were treated surgically and post-operative follow-up revealed no recurrence. Histopathological examination of the excised lesion confirmed it to be ISC.

Conclusions: ISC is a rare localized benign disease, of which surgery seems an effective option for the definite diagnosis and treatment. Occasionally scrotal reconstruction may be required in case of extensive involvement of the scrotal skin.
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June 2019

Long-term environmental exposure to microcystins increases the risk of nonalcoholic fatty liver disease in humans: A combined fisher-based investigation and murine model study.

Environ Int 2020 05 15;138:105648. Epub 2020 Mar 15.

State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, 73 East Beijing Road, Nanjing 210008, PR China.

Microcystins (MCs) produced by cyanobacteria pose serious threats to human health. However, the contribution of long-term exposure to MCs to the development of nonalcoholic fatty liver disease (NAFLD) remains poorly documented. In this study, we estimated the environmental uptake of MCs by a small population of fishers who have lived for many years on Meiliang Bay of Lake Taihu, where cyanobacterial blooms occur frequently. Serum biochemical indices of liver function and their relationships with MC contamination in these people were also investigated. Moreover, to mimic the long-term effects of MC on the livers of fishers, an animal model was established in which mice were exposed to MC-LR at an environmentally relevant level, a reference level (the no-observed adverse effect level, NOAEL), and three times the NOAEL through drinking water for 12 months. We estimated the total daily intake of MCs by fishers through contaminated lake water and food to be 5.95 μg MC-LReq, far exceeding the tolerable daily intake (2.40 μg MC-LReq) proposed by the World Health Organization (WHO). More than 80% of participants had at least one abnormal serum marker. The indices of aspartate aminotransferase (AST)/alanine aminotransferase (ALT), triglyceride (TG), globulin (GLB), and lactate dehydrogenase (LDH) had close positive associations with MC contamination, indicating that both liver damage and lipid metabolism dysfunction were induced by chronic MC exposure. Furthermore, the animal experimental results showed that long-term exposure to MC-LR at the environmentally relevant level led to hepatic steatosis with molecular alterations in circadian rhythm regulation, lipid metabolic processes, and the cell cycle pathway. Exposure to MC-LR at or above the NOAEL worsened the pathological phenotype towards nonalcoholic steatohepatitis disease (NASH) or fibrosis. These results suggest that prolonged exposure to the reference level (NOAEL) of MC-LR could cause severe liver injury to mammals. People with long-term environmental exposure to MCs might be at high risk for developing NAFLD.
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http://dx.doi.org/10.1016/j.envint.2020.105648DOI Listing
May 2020

FMNL3 regulates FASCIN for actin-mediated spindle migration and cytokinesis in mouse oocytes†.

Biol Reprod 2020 05;102(6):1203-1212

College of Animal Science and Technology, Nanjing Agricultural University, Weigang 1, Nanjing, China.

Formin-like 3 (FMNL3) is a member of the formin-likes (FMNLs), which belong to the formin family. As an F-actin nucleator, FMNL3 is essential for several cellular functions, such as polarity control, invasion, and migration. However, the roles of FMNL3 during oocytes meiosis remain unclear. In this study, we investigated the functions of FMNL3 during mouse oocyte maturation. Our results showed that FMNL3 mainly concentrated in the oocyte cortex and spindle periphery. Depleting FMNL3 led to the failure of polar body extrusion, and we also found large polar bodies in the FMNL3-deleted oocytes, indicating the occurrence of symmetric meiotic division. There was no effect of FMNL3 on spindle organization; however, we observed spindle migration defects at late metaphase I, which might be due to the decreased cytoplasmic actin. Microinjecting Fmnl3-EGFP mRNA into Fmnl3-depleted oocytes significantly rescued these defects. In addition, the results of co-immunoprecipitation and the perturbation of protein expression experiments suggested that FMNL3 interacted with the actin-binding protein FASCIN for the regulation of actin filaments in oocytes. Thus, our results provide the evidence that FMNL3 regulates FASCIN for actin-mediated spindle migration and cytokinesis during mouse oocyte meiosis.
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http://dx.doi.org/10.1093/biolre/ioaa033DOI Listing
May 2020

A Tri-Stable Piezoelectric Vibration Energy Harvester for Composite Shape Beam: Nonlinear Modeling and Analysis.

Sensors (Basel) 2020 Mar 2;20(5). Epub 2020 Mar 2.

College of Mechanical Engineering, Xi'an University of Science and Technology, Xi'an 710054, China.

To reveal the nonlinear mechanism of the tri-stable piezoelectric vibration energy harvester based on composite shape beam (TPEH-C) and its influence on the system response, the nonlinear restoring force and the nonlinear magnetic force are discussed and analyzed in this paper. The nonlinear magnetic model is acquired by using equivalent magnetizing current theory, and the nonlinear resilience model is obtained by fitting experimental data. The corresponding distributed parameter model based on generalized Hamiltonian variation principle has been established. Frequency response functions for the TPEH-C are derived according to harmonic balance expansion, and the influence of different magnet distances and different excitation accelerations on the response amplitude and bandwidth of the TPEH-C are investigated. More importantly, the correctness of the theoretical analysis is verified by experiments. The results reveal that the spectrum of composite beam shows hard characteristic and the depth of potential well is changed, which provides a new way to ameliorate the potential well of the TPEH-C. A suitable magnet distance enables the TPEH-C to improve the response amplitude and the effective frequency range. The results in this paper have a theoretical guiding significance for the optimal design and engineering application of the TPEH-C.
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http://dx.doi.org/10.3390/s20051370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085764PMC
March 2020

Protective Effects of Cytomegalovirus DNA Copies ≧1000/mL for AML Patients in Complete Remission After Single Cord Blood Transplantation.

Infect Drug Resist 2020 7;13:373-383. Epub 2020 Feb 7.

Department of Hematology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui, People's Republic of China.

Introduction: Current consensus recommends a protective effect of cytomegalovirus (CMV) infection on relapse after peripheral blood or bone marrow hematopoietic stem cell transplantation. However, in cord blood transplantation (CBT), studies of CMV infection, especially CMV viral load, on relapse are limited.

Patients And Methods: Wct e retrospectively analyzed the effect of CMV infection on 3-year outcomes in 249 AML patients according to CMV DNA load (DNA copies <1000/mL and DNA copies ≧1000/mL) within 100 days after CBT. Furthermore, eight-colour flow cytometry was used to detect peripheral blood lymphocyte subsets in 38 patients who received CBT in the last year, and 10 healthy volunteers were included as controls.

Results: The results showed that CMV DNA load did not affect the cumulative incidence of relapse in the whole study population. However, in patients with complete remission status before transplantation, the high CMV DNA load group showed a significantly reduction of relapse than the low CMV DNA load group (3.9% vs 14.6%, p=0.012, respectively), which was confirmed by multivariate analysis (HR 0.23; 95% CI, 0.07-0.73, p = 0.012). Surprisingly, high or low CMV DNA load did not significantly affect non-relapse mortality or overall survival (18.0% vs 17.0%, p=0.777 and 79.0% vs 74.6%, p=0.781, respectively). Besides, the absolute number of CD8 T cells were increased in the high CMV DNA load group compared with the low DNA load group 1 month after CBT (0.20×10/L vs 0.10×10/L, p=0.021, respectively).

Conclusion: DNA copies ≧1000/mL for AML patients in complete remission was associated with a lower incidence of relapse after CBT, which might partly result from the expansion of CMV-related CD8 T cells.
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http://dx.doi.org/10.2147/IDR.S225465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012225PMC
February 2020

Effects and long-term follow-up of using umbilical cord blood-derived mesenchymal stromal cells in pediatric patients with severe BK virus-associated late-onset hemorrhagic cystitis after unrelated cord blood transplantation.

Pediatr Transplant 2020 03 16;24(2):e13618. Epub 2020 Jan 16.

Department of Hematology of Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China.

This is a retrospective study to evaluate the efficacy and safety of umbilical cord blood-derived mesenchymal stromal cells (MSCs) for the treatment of pediatric patients with severe BK virus-associated late-onset hemorrhagic cystitis (BKV-HC) after unrelated cord blood transplantation (UCBT). Thirteen pediatric patients with severe BKV-HC from December 2013 to December 2015 were treated with MSCs. The number of MSCs transfused in each session was 1 × 10 /kg once a week until the symptoms improved. The median follow-up time was 1432 (89-2080) days. The median frequency of MSC infusion was 2 (1-3), with eight cured cases and five effective cases; the total efficacy rate was 100%. The copy number of urine BKV DNA was 4.43 (0.36-56.9) ×10 /mL before MSC infusion and 2.67 (0-56.3) ×10 /mL after MSC infusion; the difference was not significant (P = .219). There were no significant differences in the overall survival, disease-free survival, and the incidence of relapse and acute and chronic graft-versus-host disease between the MSC infusion group and non-MSC infusion group. There was also no significant difference in the cytomegalovirus, Epstein-Barr virus (EBV), and fungal and bacterial infection rates between the two groups. Although umbilical cord blood-derived MSCs do not reduce the number of BKV DNA copies in the urine, the cells have a high efficacy rate and minimal side effects in treating severe BKV-HC after UCBT among pediatric patients. MSCs do not affect the rates of relapse, long-term infection, or survival of patients with leukemia.
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http://dx.doi.org/10.1111/petr.13618DOI Listing
March 2020

Inhibition of N-WASP affects actin-mediated cytokinesis during porcine oocyte maturation.

Theriogenology 2020 Mar 7;144:132-138. Epub 2020 Jan 7.

College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address:

N-WASP is the mammalian ortholog of WASP which is an actin nucleation promoting factor and has been reported to regulate actin nucleation and polymerization for multiple cell activities. However, the expression and functions of N-WASP in porcine oocytes are still unclear. In this study, we showed that N-WASP expressed at all stages during porcine oocyte maturation, and immunofluorescence staining indicated that N-WASP mainly accumulated at the cortex in different stages of meiosis. Inhibition of N-WASP activity by Wiskostatin significantly decreased the rate of first polar body extrusion and disturbed the cell cycle progression of porcine oocytes. Further analysis indicated that cortical actin distribution was interfered by N-WASP inhibition, and this might be through its regulatory roles on the expression and localization of ARP2, a key component of actin nucleator Arp2/3 complex. Moreover, the expression of N-WASP decreased after ROCK activity inhibition, indicating a ROCK-N-WASP-ARP2/3 pathway for actin assembly in porcine oocytes. Taken together, these results suggest that N-WASP is critical for the regulation of actin filaments for cytokinesis during porcine oocyte maturation.
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http://dx.doi.org/10.1016/j.theriogenology.2020.01.005DOI Listing
March 2020

Hypoxia-inducible factor 1α (HIF-1α) mediates the epithelial-mesenchymal transition in benign prostatic hyperplasia.

Int J Clin Exp Pathol 2019 1;12(1):295-304. Epub 2019 Jan 1.

Department of Urology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine Shanghai, China.

Background: Epithelial-mesenchymal transition (EMT) based cancer cell invasion and metastasis has been thoroughly studied in prostate cancer. It was well known that EMT markers which have been found in benign prostatic hyperplasia (BPH) tissues, but system descriptions have not been described.

Methods: First, in order to construct the epithelial cells to mesenchymal cell transformation model, BPH-1 cells were cultured with supernatant of prostate matrix normal prostate stromal WPMY-1 cells, after obtaining the culture medium through a filter. After that, we observed the morphology of cells cultured for a period of time by microscopy, detected cell invasion ability by transwell assay, detected cell proliferation ability by MTT, and detected EMT marker expression by western. Finally, we treated the cells with anti-HIF-1α drugs to study their effects on EMT, and then tested several related proteins simultaneously.

Results: The results showed that the morphology of BPH-1 cells gradually changed to fusiform after cultured with WSCM. At the same time, E-cadherin and cytokeratin levels were significantly lower than those in normal medium. Simultaneous detection of vimentin (SMA) and Snail was positive compared to normal cultured cells. At the same time, the cells were cultured with WSCM and the invasive ability was up-regulated. After treatment with anti-HIF-1α drug, E-cadherin and CK5/8 protein expression was up-regulated, but vimentin, α-SMA, and Snail expression was down-regulated, and in addition, p-Smad3 protein expression was also down-regulated after anti-HIF-1α drug was added.

Conclusion: The above results indicated that WSCM-1 stromal cell supernatant WSCM can induced BPH-1 cell interstitialization, and at the same time, by inducing EMT, secreting HIF-1α activates Smad3 signaling. Our study shows that inhibition of HIF-1α expression provides a new reference for clinical treatment of BPH.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944022PMC
January 2019
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