Publications by authors named "Jiwang Zhang"

102 Publications

BCLAF1, a functional partner of BACH1, participates in DNA damage response.

DNA Repair (Amst) 2022 Jul 21;118:103371. Epub 2022 Jul 21.

College of Life Sciences, Shanghai Normal University, Guilin Road 100, Shanghai 200234, China. Electronic address:

BACH1 (Brca1-Associated C-terminal Helicase) is an important DNA damage response factor, which is involved in DNA damage repair and maintenance of genomic stability. In this study, by using tandem protein affinity purification, we have identified BCLAF1 as a novel functional partner of BACH1. BCLAF1 constitutively interacts with BACH1 regardless of DNA damage. However, in response to DNA damage, along with BACH1, BCLAF1 is recruited to the DNA damage sites and the recruitment of BCLAF1 was regulated by BACH1 and BRCA1. Interestingly, BCLAF1 deficient cells are deficient for DSB-initiated HR, but RAD51 foci formation is intact following IR treatment. Taken together, these findings reveal that BCLAF1 is a functional binding partner of BACH1 playing a key role in DNA damage response.
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http://dx.doi.org/10.1016/j.dnarep.2022.103371DOI Listing
July 2022

Mechanisms that regulate the activities of TET proteins.

Cell Mol Life Sci 2022 Jun 15;79(7):363. Epub 2022 Jun 15.

Department of Cancer Biology, Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL, 60153, USA.

The ten-eleven translocation (TET) family of dioxygenases consists of three members, TET1, TET2, and TET3. All three TET enzymes have Fe and α-ketoglutarate (α-KG)-dependent dioxygenase activities, catalyzing the 1st step of DNA demethylation by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), and further oxidize 5hmC to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Gene knockout studies demonstrated that all three TET proteins are involved in the regulation of fetal organ generation during embryonic development and normal tissue generation postnatally. TET proteins play such roles by regulating the expression of key differentiation and fate-determining genes via (1) enzymatic activity-dependent DNA methylation of the promoters and enhancers of target genes; and (2) enzymatic activity-independent regulation of histone modification. Interacting partner proteins and post-translational regulatory mechanisms regulate the activities of TET proteins. Mutations and dysregulation of TET proteins are involved in the pathogenesis of human diseases, specifically cancers. Here, we summarize the research on the interaction partners and post-translational modifications of TET proteins. We also discuss the molecular mechanisms by which these partner proteins and modifications regulate TET functioning and target gene expression. Such information will help in the design of medications useful for targeted therapy of TET-mutant-related diseases.
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http://dx.doi.org/10.1007/s00018-022-04396-xDOI Listing
June 2022

The molecular mechanism and challenge of targeting XPO1 in treatment of relapsed and refractory myeloma.

Transl Oncol 2022 Aug 1;22:101448. Epub 2022 Jun 1.

Department of Cancer Biology, Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University Medical Center, USA.

Multiple myeloma (MM) treatment regimens have vastly improved since the introduction of immunomodulators, proteasome inhibitors, and anti-CD38 monoclonal antibodies; however, MM is considered an incurable disease due to inevitable relapse and acquired drug resistance. Understanding the molecular mechanism by which drug resistance is acquired will help create novel strategies to prevent relapse and help develop novel therapeutics to treat relapsed/refractory (RR)-MM patients. Currently, only homozygous deletion/mutation of TP53 gene due to "double-hits" on Chromosome 17p region is consistently associated with a poor prognosis. The exciting discovery of XPO1 overexpression and mislocalization of its cargos in the RR-MM cells has led to a novel treatment options. Clinical studies have demonstrated that the XPO1 inhibitor selinexor can restore sensitivity of RR-MM to PIs and dexamethasone. We will elaborate on the problems of MM treatment strategies and discuss the mechanism and challenges of using XPO1 inhibitors in RR-MM therapies while deliberating potential solutions.
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http://dx.doi.org/10.1016/j.tranon.2022.101448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166471PMC
August 2022

Case Report: Two Cases of Watershed Phenomenon in Mechanical Circulatory Support Devices: Computed Tomography Angiography Imaging and Literature Review.

Front Cardiovasc Med 2022 13;9:893355. Epub 2022 May 13.

Department of Radiology, TEDA International Cardiovascular Hospital, Tianjin, China.

Mechanical circulatory support (MCS) has become a processing technique used in end-stage heart failure (ESHF) because it can significantly improve survival and quality of life in patients with ESHF as either a transitional support therapy or a permanent replacement therapy before heart transplant. However, various potential complications associated with MCS need to be considered, especially aortic root thrombus formation. It's critical to have an appropriate diagnosis of aortic root thrombus and "watershed" because the prognosis and treatment are different. Both "watershed" and aortic root thrombus formation can be characterized by computed tomography angiography. The CT manifestations of two patients who had MCS device implantation in our hospital (one with intra-aortic balloon pumps + extracorporeal membrane oxygenators, the other with left ventricular assist devices) were reported, and a literature review that recognized of "watershed" phenomenon in the aortic root was conducted.
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http://dx.doi.org/10.3389/fcvm.2022.893355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9136032PMC
May 2022

High-risk disease in newly diagnosed multiple myeloma: beyond the R-ISS and IMWG definitions.

Blood Cancer J 2022 05 30;12(5):83. Epub 2022 May 30.

Department of Hematology/Oncology, Loyola University Medical Center, Maywood, IL, 60153, USA.

Multiple myeloma (MM) is an acquired malignant plasma cell disorder that develops late in life. Although progression free and overall survival has improved across all age, race, and ethnic groups, a subset of patients have suboptimal outcomes and are labeled as having high risk disease. A uniform approach to risk in NDMM remains elusive despite several validated risk stratification systems in clinical use. While we attempt to capture risk at diagnosis, the reality is that many important prognostic characteristics remain ill-defined as some patients relapse early who were defined as low risk based on their genomic profile at diagnosis. It is critical to establish a definition of high risk disease in order to move towards risk-adapted treatment approaches. Defining risk at diagnosis is important to both effectively design future clinical trials and guide which clinical data is needed in routine practice. The goal of this review paper is to summarize and compare the various established risk stratification systems, go beyond the R-ISS and international myeloma working group risk stratifications to evaluate specific molecular and cytogenetic abnormalities and how they impact prognosis independently. In addition, we explore the wealth of new genomic information from recent whole genome/exome sequencing as well as gene expression data and review known clinical factors affecting outcome such as disease burden and early relapse as well as patient related factors such as race. Finally, we provide an outlook on developing a new high risk model system and how we might make sense of co-occurrences, oncogenic dependencies, and mutually exclusive mutations.
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http://dx.doi.org/10.1038/s41408-022-00679-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9151761PMC
May 2022

Increasing genomic discovery in newly diagnosed multiple myeloma: defining disease biology and its correlation to risk.

Ann Hematol 2022 Jul 18;101(7):1407-1420. Epub 2022 May 18.

Department of Cancer Biology, Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL, 60153, USA.

Our understanding of MM genomics has expanded rapidly in the past 5-10 years as a consequence of cytogenetic analyses obtained in routine clinical practice as well as the ability to perform whole-exome/genome sequencing and gene expression profiling on large patient data sets. This knowledge has offered new insights into disease biology and is increasingly defining high-risk genomic patterns. In this manuscript, we present a thorough review of our current knowledge of MM genomics. The epidemiology and biology of chromosomal abnormalities including both copy number abnormalities and chromosomal translocation are described in full with a focus on those most clinically impactful such as 1q amplification and del(17p) as well as certain chromosome 14 translocations. A review of our ever-expanding knowledge of genetic mutations derived from recent whole-genome/exome data sets is then reviewed including those that drive disease pathogenesis from precursor states as well as those that may impact clinical outcomes. We then transition and attempt to elucidate how both chromosomal abnormalities and gene mutations are evolving our understanding of disease risk. We conclude by offering our perspectives moving forward as to how we might apply whole-genome/exome-level data in addition to routine cytogenetic analyses to improve patient outcomes as well as further knowledge gaps that must be addressed.
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http://dx.doi.org/10.1007/s00277-022-04856-1DOI Listing
July 2022

Ripk3 signaling regulates HSCs during stress and represses radiation-induced leukemia in mice.

Stem Cell Reports 2022 06 12;17(6):1428-1441. Epub 2022 May 12.

Department of Cancer Biology, Oncology Research Institute, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL 60153, USA; Department of Radiation Oncology, Loyola University Medical Center, Maywood, IL 60153, USA; Department of Pathology, Loyola University Medical Center, Maywood, IL 60153, USA. Electronic address:

Receptor-interacting protein kinase 3 (Ripk3) is one of the critical mediators of inflammatory cytokine-stimulated signaling. Here we show that Ripk3 signaling selectively regulates both the number and the function of hematopoietic stem cells (HSCs) during stress conditions. Ripk3 signaling is not required for normal homeostatic hematopoiesis. However, in response to serial transplantation, inactivation of Ripk3 signaling prevents stress-induced HSC exhaustion and functional HSC attenuation, while in response to fractionated low doses of ionizing radiation (IR), inactivation of Ripk3 signaling accelerates leukemia/lymphoma development. In both situations, Ripk3 signaling is primarily stimulated by tumor necrosis factor-α. Activated Ripk3 signaling promotes the elimination of HSCs during serial transplantation and pre-leukemia stem cells (pre-LSCs) during fractionated IR by inducing Mlkl-dependent necroptosis. Activated Ripk3 signaling also attenuates HSC functioning and represses a pre-LSC-to-LSC transformation by promoting Mlkl-independent senescence. Furthermore, we demonstrate that Ripk3 signaling induces senescence in HSCs and pre-LSCs by attenuating ISR-mediated mitochondrial quality control.
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http://dx.doi.org/10.1016/j.stemcr.2022.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213819PMC
June 2022

Exogenous 6-Benzyladenine Improved the Ear Differentiation of Waterlogged Summer Maize by Regulating the Metabolism of Hormone and Sugar.

Front Plant Sci 2022 7;13:848989. Epub 2022 Apr 7.

State Key Laboratory of Crop Biology and College of Agronomy, Shandong Agricultural University, Tai'an, China.

Waterlogging (W-B) is a major abiotic stress during the growth cycle of maize production in Huang-huai-hai plain of China, threatening food security. A wide range of studies suggests that the application of 6-benzyladenine (6-BA) can mitigate the W-B effects on crops. However, the mechanisms underlying this process remain unclear. In this study, the application of 6-BA that effectively increased the yield of summer maize was confirmed to be related to the hormone and sugar metabolism. At the florets differentiation stage, application of 6-BA increased the content of trans-zeatin (TZ, + 59.3%) and salicylic acid (SA, + 285.5%) of ears to induce the activity of invertase, thus establishing sink strength. During the phase of sexual organ formation, the TZ content of ear leaves, spike nodes, and ears was increased by 24.2, 64.2, and 46.1%, respectively, in W-B treatment, compared with that of W. Accordingly, the sugar metabolism of summer maize was also improved. Therefore, the structure of the spike node was improved, promoting the translocation of carbon assimilations toward the ears and the development of ears and filaments. Thus the number of fertilized florets, grain number, and yield were increased by the application of 6-BA.
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http://dx.doi.org/10.3389/fpls.2022.848989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021890PMC
April 2022

Molecular mechanisms by which splice modulator GEX1A inhibits leukaemia development and progression.

Br J Cancer 2022 07 14;127(2):223-236. Epub 2022 Apr 14.

Department of Cancer Biology, Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL, USA.

Introduction: Splice modulators have been assessed clinically in treating haematologic malignancies exhibiting splice factor mutations and acute myeloid leukaemia. However, the mechanisms by which such modulators repress leukaemia remain to be elucidated.

Objectives: The primary goal of this assessment was to assess the molecular mechanism by which the natural splice modulator GEX1A kills leukaemic cells in vitro and within in vivo mouse models.

Methods: Using human leukaemic cell lines, we assessed the overall sensitivity these cells have to GEX1A via EC analysis. We subsequently analysed its effects using in vivo xenograft mouse models and examined whether cell sensitivities were correlated to genetic characteristics or protein expression levels. We also utilised RT-PCR and RNAseq analyses to determine splice change and RNA expression level differences between sensitive and resistant leukaemic cell lines.

Results: We found that, in vitro, GEX1A induced an MCL-1 isoform shift to pro-apoptotic MCL-1S in all leukaemic cell types, though sensitivity to GEX1A-induced apoptosis was negatively associated with BCL-xL expression. In BCL-2-expressing leukaemic cells, GEX1A induced BCL-2-dependent apoptosis by converting pro-survival BCL-2 into a cell killer. Thus, GEX1A + selective BCL-xL inhibition induced synergism in killing leukaemic cells, while GEX1A + BCL-2 inhibition showed antagonism in BCL-2-expressing leukaemic cells. In addition, GEX1A sensitised FLT3-ITD leukaemic cells to apoptosis by inducing aberrant splicing and repressing the expression of FLT3-ITD. Consistently, in in vivo xenografts, GEX1A killed the bulk of leukaemic cells via apoptosis when combined with BCL-xL inhibition. Furthermore, GEX1A repressed leukaemia development by targeting leukaemia stem cells through inhibiting FASTK mitochondrial isoform expression across sensitive and non-sensitive leukaemia types.

Conclusion: Our study suggests that GEX1A is a potent anti-leukaemic agent in combination with BCL-xL inhibitors, which targets leukaemic blasts and leukaemia stem cells through distinct mechanisms.
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http://dx.doi.org/10.1038/s41416-022-01796-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296642PMC
July 2022

The role of TBK1 in cancer pathogenesis and anticancer immunity.

J Exp Clin Cancer Res 2022 Apr 9;41(1):135. Epub 2022 Apr 9.

Department of Cancer Biology, Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL, 60153, USA.

The TANK-binding kinase 1 (TBK1) is a serine/threonine kinase belonging to the non-canonical inhibitor of nuclear factor-κB (IκB) kinase (IKK) family. TBK1 can be activated by pathogen-associated molecular patterns (PAMPs), inflammatory cytokines, and oncogenic kinases, including activated K-RAS/N-RAS mutants. TBK1 primarily mediates IRF3/7 activation and NF-κB signaling to regulate inflammatory cytokine production and the activation of innate immunity. TBK1 is also involved in the regulation of several other cellular activities, including autophagy, mitochondrial metabolism, and cellular proliferation. Although TBK1 mutations have not been reported in human cancers, aberrant TBK1 activation has been implicated in the oncogenesis of several types of cancer, including leukemia and solid tumors with KRAS-activating mutations. As such, TBK1 has been proposed to be a feasible target for pharmacological treatment of these types of cancer. Studies suggest that TBK1 inhibition suppresses cancer development not only by directly suppressing the proliferation and survival of cancer cells but also by activating antitumor T-cell immunity. Several small molecule inhibitors of TBK1 have been identified and interrogated. However, to this point, only momelotinib (MMB)/CYT387 has been evaluated as a cancer therapy in clinical trials, while amlexanox (AMX) has been evaluated clinically for treatment of type II diabetes, nonalcoholic fatty liver disease, and obesity. In this review, we summarize advances in research into TBK1 signaling pathways and regulation, as well as recent studies on TBK1 in cancer pathogenesis. We also discuss the potential molecular mechanisms of targeting TBK1 for cancer treatment. We hope that our effort can help to stimulate the development of novel strategies for targeting TBK1 signaling in future approaches to cancer therapy.
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http://dx.doi.org/10.1186/s13046-022-02352-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8994244PMC
April 2022

SIRT2 regulates proliferation and chemotherapy response of MLL-ENL-driven acute myeloid leukemia.

Biochem Biophys Res Commun 2022 03 25;596:36-42. Epub 2022 Jan 25.

Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, 280 S. Chongqing Road, Shanghai, 200025, China. Electronic address:

Both MLL-AF9 and MLL-ENL leukemia fusion proteins drive oncogenic transformation of hematopoietic cells through their N-terminal DNA/histone binding mixed-lineage leukemia 1 domain and C-terminal fragment of AF9 or ENL containing an unstructured linker region and the ANC1 homology domain, which recruits transcription factors. Despite of their structural similarity, acute myeloid leukemia (AML) patients bearing MLL-ENL show more adverse outcomes compared to those with MLL-AF9. We recapitulated the clinical patterns of these two MLL-fusions driven AMLs using murine models and found that MLL-ENL AML cells showed slower cell cycle progression and more resistance to standard chemotherapy than MLL-AF9 cells. These phenotypes were primarily controlled by the linker regions of ENL and a highly conserved lysine residue K469 within. Substitution of K469 with an acetylated mimic glutamine abolished the ability of MLL-ENL to suppress proliferation and promote chemo-resistance. We showed that deacetylase Sirt2 might act as an upstream regulator of MLL-ENL. Deletion of Sirt2 promoted proliferation of AML cells with either MLL fusions. Importantly, loss of Sirt2 greatly enhanced the sensitivity of the MLL-ENL AML cells to chemo-treatment. Taken together, our study uncovered a unique regulatory role of Sirt2 in leukemogenesis and suggested targeting SIRT2 as a new way to sensitize MLL-ENL AML patience for chemotherapy.
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http://dx.doi.org/10.1016/j.bbrc.2022.01.081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052174PMC
March 2022

6-Benzyladenine increasing subsequent waterlogging-induced waterlogging tolerance of summer maize by increasing hormone signal transduction.

Ann N Y Acad Sci 2022 03 11;1509(1):89-112. Epub 2021 Nov 11.

State Key Laboratory of Crop Biology and College of Agronomy, Shandong Agricultural University, Taian, Shandong, PR China.

Summer maize is frequently subjected to waterlogging damage because of increased and variable rainfall during the growing season. The application of 6-benzyladenine (6-BA) can effectively mitigate the waterlogging effects on plant growth and increase the grain yield of waterlogged summer maize. However, the mechanisms underlying this process and the involvement of 6-BA in relevant signal transduction pathways remain unclear. In this study, we explored the effects of 6-BA on waterlogged summer maize using a phosphoproteomic technique to better understand the mechanism by which summer maize growth improves following waterlogging. Application of 6-BA inhibited the waterlogging-induced increase in abscisic acid (ABA) content and increased the phosphorylation levels of proteins involved in ABA signaling; accordingly, stomatal responsiveness to exogenous ABA increased. In addition, the application of 6-BA had a long-term effect on signal transduction pathways and contributed to rapid responses to subsequent stresses. Plants primed with 6-BA accumulated more ethylene and jasmonic acid in response to subsequent waterlogging; accordingly, leaf SPAD, antioxidase activity, and root traits improved by 6-BA priming. These results suggest that the effects of 6-BA on hormone signal transduction pathways are anamnestic, which enables plants to show faster or stronger defense responses to stress.
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http://dx.doi.org/10.1111/nyas.14708DOI Listing
March 2022

RIPK3 signaling and its role in the pathogenesis of cancers.

Cell Mol Life Sci 2021 Dec 15;78(23):7199-7217. Epub 2021 Oct 15.

Department of Cancer Biology, Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL, 60153, USA.

RIPK3 (receptor-interacting protein kinase 3) is a serine/threonine-protein kinase. As a key component of necrosomes, RIPK3 is an essential mediator of inflammatory factors (such as TNFα-tumor necrosis factor α) and infection-induced necroptosis, a programmed necrosis. In addition, RIPK3 signaling is also involved in the regulation of apoptosis, cytokine/chemokine production, mitochondrial metabolism, autophagy, and cell proliferation by interacting with and/or phosphorylating the critical regulators of the corresponding signaling pathways. Similar to apoptosis, RIPK3-signaling-mediated necroptosis is inactivated in most types of cancers, suggesting RIPK3 might play a critical suppressive role in the pathogenesis of cancers. However, in some inflammatory types of cancers, such as pancreatic cancers and colorectal cancers, RIPK3 signaling might promote cancer development by stimulating proliferation signaling in tumor cells and inducing an immunosuppressive response in the tumor environment. In this review, we summarize recent research progress in the regulators of RIPK3 signaling, and discuss the function of this pathway in the regulation of mixed lineage kinase domain-like (MLKL)-mediated necroptosis and MLKL-independent cellular behaviors. In addition, we deliberate the potential roles of RIPK3 signaling in the pathogenesis of different types of cancers and discuss the potential strategies for targeting this pathway in cancer therapy.
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http://dx.doi.org/10.1007/s00018-021-03947-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9044760PMC
December 2021

HDAC1 is required for GATA-1 transcription activity, global chromatin occupancy and hematopoiesis.

Nucleic Acids Res 2021 09;49(17):9783-9798

Department of Cellular and Molecular Physiology, Hershey, PA 17033, USA.

The activity of hematopoietic factor GATA-1 is modulated through p300/CBP-mediated acetylation and FOG-1 mediated indirect interaction with HDAC1/2 containing NuRD complex. Although GATA-1 acetylation is implicated in GATA-1 activation, the role of deacetylation is not studied. Here, we found that the FOG-1/NuRD does not deacetylate GATA-1. However, HDAC1/2 can directly bind and deacetylate GATA-1. Two arginine residues within the GATA-1 linker region mediates direct interaction with HDAC1. The arginine to alanine mutation (2RA) blocks GATA-1 deacetylation and fails to induce erythroid differentiation. Gene expression profiling and ChIP-seq analysis further demonstrate the importance of GATA-1 deacetylation for gene activation and chromatin recruitment. GATA-12RA knock-in (KI) mice suffer mild anemia and thrombocytopenia with accumulation of immature erythrocytes and megakaryocytes in bone marrow and spleen. Single cell RNA-seq analysis of Lin- cKit+ (LK) cells further reveal a profound change in cell subpopulations and signature gene expression patterns in HSC, myeloid progenitors, and erythroid/megakaryocyte clusters in KI mice. Thus, GATA-1 deacetylation and its interaction with HDAC1 modulates GATA-1 chromatin binding and transcriptional activity that control erythroid/megakaryocyte commitment and differentiation.
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http://dx.doi.org/10.1093/nar/gkab737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464053PMC
September 2021

The Fetal-to-Adult Hematopoietic Stem Cell Transition and its Role in Childhood Hematopoietic Malignancies.

Stem Cell Rev Rep 2021 12 23;17(6):2059-2080. Epub 2021 Aug 23.

Department of Cancer Biology, Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL, 60153, USA.

As with most organ systems that undergo continuous generation and maturation during the transition from fetal to adult life, the hematopoietic and immune systems also experience dynamic changes. Such changes lead to many unique features in blood cell function and immune responses in early childhood. The blood cells and immune cells in neonates are a mixture of fetal and adult origin due to the co-existence of both fetal and adult types of hematopoietic stem cells (HSCs) and progenitor cells (HPCs). Fetal blood and immune cells gradually diminish during maturation of the infant and are almost completely replaced by adult types of cells by 3 to 4 weeks after birth in mice. Such features in early childhood are associated with unique features of hematopoietic and immune diseases, such as leukemia, at these developmental stages. Therefore, understanding the cellular and molecular mechanisms by which hematopoietic and immune changes occur throughout ontogeny will provide useful information for the study and treatment of pediatric blood and immune diseases. In this review, we summarize the most recent studies on hematopoietic initiation during early embryonic development, the expansion of both fetal and adult types of HSCs and HPCs in the fetal liver and fetal bone marrow stages, and the shift from fetal to adult hematopoiesis/immunity during neonatal/infant development. We also discuss the contributions of fetal types of HSCs/HPCs to childhood leukemias.
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http://dx.doi.org/10.1007/s12015-021-10230-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9059172PMC
December 2021

Effects of Urea-Ammonium Nitrate Solution on Yield, NO Emission, and Nitrogen Efficiency of Summer Maize Under Integration of Water and Fertilizer.

Front Plant Sci 2021 3;12:700331. Epub 2021 Aug 3.

State Key Laboratory of Crop Biology and College of Agronomy, Shandong Agricultural University, Tai'an, China.

In order to clarify the effects of urea-ammonium nitrate solution (UAN) on the yield, nitrogen-use efficiency (NUE), and NO emissions of summer maize under the condition of water and fertilizer integration, different types of nitrogen fertilizer were selected, namely, ordinary urea (urea) and UAN. Our results showed that the application of UAN was beneficial to improve the dry matter accumulation and the distribution of summer maize. Compared with urea treatment, the total nitrogen accumulation of UAN treatment was increased by 15.8%, and the harvest index was increased by 5.5%. The partial productivity, agronomic use efficiency, and recovery rate of nitrogen for UAN treatment were also increased by 9.1, 19.8, and 31.2%, respectively, compared to those of urea treatment. The soil nitrogen dependence rate treated with UAN was significantly decreased by 13.6%, compared to that of urea treatment. In addition, UAN was beneficial to reduce NO emissions. The NO warming potential (GWP) and NO greenhouse gas intensity (GHGI) of urea treatment were 39.3 and 52.4% higher, compared to those of UAN treatment. The improvement of dry matter accumulation and distribution and nitrogen efficiency for UAN treatment were beneficial to increase the grain yield by 9.1%, compared to that of urea treatment. In conclusion, under the fertigation, the application of UAN favors higher yield and nitrogen uptake, with less soil nitrogen residue, higher NUE, and better environmental effect.
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http://dx.doi.org/10.3389/fpls.2021.700331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369924PMC
August 2021

Responses of nitrogen efficiency and antioxidant system of summer maize to waterlogging stress under different tillage.

PeerJ 2021 26;9:e11834. Epub 2021 Jul 26.

Shandong Agricultural University, Taian, China.

Waterlogging was one of the main abiotic stresses affecting maize yield and growth in the North China Plain, while ridge tillage effectually improved soil environment, enhanced crop stress resistance to waterlogging, and increased grain yield of waterlogged maize. In order to explore the responses of nitrogen (N) efficiency and antioxidant system of summer maize to waterlogging stress under different tillage, a field experiment was conducted to explore N use efficiency, leaf activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), and malondialdehyde (MDA) content of waterlogged maize Denghai 605 (DH605) and Zhengdan 958 (ZD958) under different tillage system (ridge planting and flat planting). Our results showed that ridge tillage was beneficial to ameliorate waterlogging damages on antioxidant system by increasing SOD, POD, and CAT activities, and decreasing MDA content. Moreover, ridge tillage significantly increased N efficiency of waterlogged maize. N translocation amount (NTA), N translocation efficiency (NTE), N contribution proportion (NCP), N harvest index (NHI), and N use efficiency (NUE) of waterlogging treatment under ridge planting system (W-V3+R) for DH605 was increased by 108%, 69%, 60%, 8% and 16%, while ZD958 increased by 248%, 132%, 146%, 13% and 16%, respectively, compared to those of waterlogging treatment under flat planting system (W-V3). Ultimately, ridge tillage led to a significant yield improvement by 39% and 50% for DH605 and ZD958, respectively, compared to that of W-V3. In conclusion, ridge tillage was conducive to retard leaf aging, and enhance nitrogen efficiency, thereby resulting in a yield improvement of waterlogged summer maize.
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http://dx.doi.org/10.7717/peerj.11834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320525PMC
July 2021

Tumor Microenvironment-Derived R-spondins Enhance Antitumor Immunity to Suppress Tumor Growth and Sensitize for Immune Checkpoint Blockade Therapy.

Cancer Discov 2021 12;11(12):3142-3157

Divisions of Pathology and Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Natural killer (NK) cells and T cells are key effectors of antitumor immune responses and major targets of checkpoint inhibitors. In multiple cancer types, we find that the expression of Wnt signaling potentiator R-spondin genes (e.g., RSPO3) is associated with favorable prognosis and positively correlates with gene signatures of both NK cells and T cells. Although endothelial cells and cancer-associated fibroblasts comprise the R-spondin 3-producing cells, NK cells and T cells correspondingly express the R-spondin 3 receptor LGR6 within the tumor microenvironment (TME). Exogenous expression or intratumor injection of R-spondin 3 in tumors enhanced the infiltration and function of cytotoxic effector cells, which led to tumor regression. NK cells and CD8+ T cells independently and cooperatively contributed to R-spondin 3-induced control of distinct tumor types. The effect of R-spondin 3 was mediated in part through upregulation of MYC and ribosomal biogenesis. Importantly, R-spondin 3 expression enhanced tumor sensitivity to anti-PD-1 therapy, thereby highlighting new therapeutic avenues.

Significance: Our study identifies novel targets in enhancing antitumor immunity and sensitizing immune checkpoint inhibition, which provides a rationale for developing new immunotherapies against cancers. It also offers mechanistic insights on Wnt signaling-mediated modulation of anticancer immunity in the TME and implications for a putative R-spondin-LGR6 axis in regulating NK-cell biology. This article is highlighted in the In This Issue feature, p. 2945.
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http://dx.doi.org/10.1158/2159-8290.CD-20-0833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8716674PMC
December 2021

Role of c-Myc haploinsufficiency in the maintenance of HSCs in mice.

Blood 2021 02;137(5):610-623

Department of Medicine and.

This study was conducted to determine the dosage effect of c-Myc on hematopoiesis and its distinct role in mediating the Wnt/β-catenin pathway in hematopoietic stem cell (HSC) and bone marrow niche cells. c-Myc haploinsufficiency led to ineffective hematopoiesis by inhibiting HSC self-renewal and quiescence and by promoting apoptosis. We have identified Nr4a1, Nr4a2, and Jmjd3, which are critical for the maintenance of HSC functions, as previously unrecognized downstream targets of c-Myc in HSCs. c-Myc directly binds to the promoter regions of Nr4a1, Nr4a2, and Jmjd3 and regulates their expression. Our results revealed that Nr4a1 and Nr4a2 mediates the function of c-Myc in regulating HSC quiescence, whereas all 3 genes contribute to the function of c-Myc in the maintenance of HSC survival. Adenomatous polyposis coli (Apc) is a negative regulator of the Wnt/β-catenin pathway. We have provided the first evidence that Apc haploinsufficiency induces a blockage of erythroid lineage differentiation through promoting secretion of IL6 in bone marrow endothelial cells. We found that c-Myc haploinsufficiency failed to rescue defective function of Apc-deficient HSCs in vivo but it was sufficient to prevent the development of severe anemia in Apc-heterozygous mice and to significantly prolong the survival of those mice. Furthermore, we showed that c-Myc-mediated Apc loss induced IL6 secretion in endothelial cells, and c-Myc haploinsufficiency reversed the negative effect of Apc-deficient endothelial cells on erythroid cell differentiation. Our studies indicate that c-Myc has a context-dependent role in mediating the function of Apc in hematopoiesis.
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http://dx.doi.org/10.1182/blood.2019004688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215193PMC
February 2021

Short-Term Flexural Stiffness Prediction of CFRP Bars Reinforced Coral Concrete Beams.

Materials (Basel) 2021 Jan 19;14(2). Epub 2021 Jan 19.

College of Civil Engineering and Architecture, Guilin University of Technology, Guilin 541004, China.

FRP (Fiber Reinforced Polymer) Bar reinforced coral concrete beam is a new type of structural member that has been used more and more widely in marine engineering in recent years. In order to study and predict the flexural performance of CFRP reinforced coral concrete beams, the flexural rigidity, crack morphology and failure mode of concrete were studied in detail. The results show that under the condition of similar reinforcement ratio, the flexural rigidity of CFRP reinforced coral concrete beam is significantly lower than that of ordinary reinforced concrete beam. Increasing the cross-section reinforcement ratio within a certain range can increase the bending stiffness of the test beam or reduce the deflection, but the strength utilization rate of CFRP reinforcement is greatly reduced. The short-term bending stiffness of the CFRP reinforced coral concrete beam calculated by the existing standard formula is obviously higher. This paper proposes a modified formula for introducing the strain inhomogeneity coefficient () of CFRP bars and considers the relative slip between CFRP bars and coral concrete to predict the short-term flexural stiffness of coral concrete beams reinforced by CFRP bars. The formula was verified with the test results, and it was proved that the formula has a good consistency with the test results.
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http://dx.doi.org/10.3390/ma14020467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836010PMC
January 2021

Narrowing Yield Gaps and Enhancing Nitrogen Utilization for Summer Maize ( by Combining the Effects of Varying Nitrogen Fertilizer Input and Planting Density in DSSAT Simulations.

Front Plant Sci 2020 16;11:560466. Epub 2020 Nov 16.

State Key Laboratory of Crop Biology, College of Agronomy, Shandong Agricultural University, Tai'an, China.

In China, the most common grain crop is maize (). The increasing pressure to meet the food demands of its growing population has pushed Chinese maize farmers toward an excessive use of chemical fertilizers, a practice which ultimately leads to a massive waste of resources and widespread environmental pollution. As a result, increasing the yield and improving the nitrogen (N) use efficiency of maize has become a critical issue for agriculture in China. This study, which analyzes the combined data from a simulation carried out using the Decision Support System for Agrotechnology Transfer (DSSAT), a field experiment, and a household survey, explored the effectiveness of several approaches aimed at narrowing the maize yield gap and improving the N utilization efficiency in the Huang-Huai-Hai Plain (HHHP), the most important area for the production of summer maize in China. The various approaches we studied deploy different methods for the integrated management of N fertilizer input and the planting density. The study produced the following results: (1) For the simulated and actual maize yields, the root mean square error (RMSE), the normalized root mean squared errors (NRMSE) and the index of agreement (d) were 1,171 (kg ha), 12% and 0.84, respectively. These results show that the model is viable for the experiment included in the study; (2) The potential yield was 15.58 t ha, and the yields achieved by the super-high-yield cultivation pattern (SH), the optimized nutrient and density management pattern (ONM), the simulated farmer's practice cultivation pattern (FP) and actual farmer's practice (AFP) were 11.43, 11.06, 10.33, and 7.95 t ha, respectively. The yield gaps associated with the different yield levels were large; (3) For summer maize, the high yield and a high N partial factor productivity (NPFP) was found when applying a planting density of 9 plants m and an N application amount of 246 kg ha. These results suggest that the maximum yield that can actually be achieved by optimizing the N application and planting density is less than 73% of the potential yield. This implies in turn that in order to further narrow the observed yield gaps, other factors, such as irrigation, sowing dates and pest control need to be considered.
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http://dx.doi.org/10.3389/fpls.2020.560466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707061PMC
November 2020

Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches.

J Hematol Oncol 2020 11 23;13(1):157. Epub 2020 Nov 23.

Department of Cancer Biology, Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL, 60153, USA.

Aging drives the genetic and epigenetic changes that result in a decline in hematopoietic stem cell (HSC) functioning. Such changes lead to aging-related hematopoietic/immune impairments and hematopoietic disorders. Understanding how such changes are initiated and how they progress will help in the development of medications that could improve the quality life for the elderly and to treat and possibly prevent aging-related hematopoietic diseases. Here, we review the most recent advances in research into HSC aging and discuss the role of HSC-intrinsic events, as well as those that relate to the aging bone marrow niche microenvironment in the overall processes of HSC aging. In addition, we discuss the potential mechanisms by which HSC aging is regulated.
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http://dx.doi.org/10.1186/s13045-020-00994-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686726PMC
November 2020

Improving smallholder farmers' maize yields and economic benefits under sustainable crop intensification in the North China Plain.

Sci Total Environ 2021 Apr 20;763:143035. Epub 2020 Oct 20.

State Key Laboratory of Crop Biology and College of Agronomy, Shandong Agricultural University, Tai'an 271018, Shandong, China.

To meet the food demands of a growing population, the maize production systems deployed by smallholders in China have tended towards extremely intensive planting and excessive use of fertilizers, which have caused serious environmental impacts. This study investigated the balance between the maize yield and nitrogen (N) input in the North China Plain (NCP), which is one of the most important grain-producing region in China. Our study compared yield simulations generated by the DSSAT-CERES-Maize model with actual data from a number of multi-site field experiments and an extensive household surveys encompassing 1671 farmers. The smallholders' maize cultivars, plant population, and amount of N input on the crop yield and how these affects the economic benefits were analyzed. The results showed that the average traditional farming methods' yield was 72% of the attainable yield, which means that farmers have ample room to improve their yields. We also found that the maize yields varied widely between farmers, and that most of them applied excessive amounts of N but failing to achieve an optimal yield due to poor fertilization management techniques. The study found that the economic benefits achieved by the farmers were low, but after deploying high-yield (HY) methods, the yield was increased by 34.9% and the economic benefits by 14.4%. The greenhouse gas (GHG) emissions associated with the traditional farming methods were high and could potentially be reduced by 48.6%. All in all, farmers should be given guidance on how to appropriately increase the plant population, reduce the input of N fertilizer, and optimize farmland management measures, so that China can achieve intensive but sustainable agricultural production at a lower environmental cost. It was concluded that there are still numerous biological and abiotic factors that restrict production increases by smallholders. These factors vary from region to region and require further investigation.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143035DOI Listing
April 2021

Integrating density and fertilizer management to optimize the accumulation, remobilization, and distribution of biomass and nutrients in summer maize.

Sci Rep 2020 07 16;10(1):11777. Epub 2020 Jul 16.

State Key Laboratory of Crop Biology and College of Agronomy, Shandong Agricultural University, Tai'an , 271018, Shandong, China.

Improved the utilization of fertilizer while maintaining the increased of grain yield was the focus of Chinese researchers. Nutrient uptake, distribution, and remobilization are important factors affecting the fertilizer utilization and grain yield of maize. This study aimed to provide a theoretical and practical basis for science-based, high-yielding, and high-efficiency cultivation practices by examining differences in biomass and nutrient uptake, distribution, and remobilization characteristics under three cultivation patterns. We set 12 treatments as follows: super high-yielding cultivation pattern (SH), optimized nutrient management cultivation pattern (ONM), local farmer's practice cultivation pattern (FP), and a series of nutrient omission plots, which excluded nitrogen (N), phosphorus (P), or potassium (K) from the three patterns. The results demonstrated that SH and ONM increased the yield and actual harvested ears by 35.4, 20.7 and by 20.2, 17.6%, respectively. Compared with the FP, SH and ONM increased biomass, N, P, and K accumulation at silking (R1 stage) by 24.4, 31.2, 39.4, and 34.8%, and by 21.7, 22.2, 31.7, and 34.8%, respectively. SH and ONM significantly increased biomass and nutrient distribution to the grains. ONM significantly increased N use efficiency. P and K use efficiency under the ONM pattern was significantly higher than under SH, but was lower than under the FP pattern over two years. This research demonstrates that ONM may significantly reduce fertilizer rates, effectively improve the nutrient remobilization efficiency and uptake at post-silking without negatively affecting grain yield, thereby increasing N use efficiency.
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http://dx.doi.org/10.1038/s41598-020-68730-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367288PMC
July 2020

Fatigue Crack Growth Behaviour of Precipitate-Strengthened CuNiSi Alloy under Different Loading Modes.

Materials (Basel) 2020 May 12;13(10). Epub 2020 May 12.

State Key Laboratory of Traction Power, Southwest Jiaotong University, Chengdu 610031, China.

In this study, fatigue crack tests of CuNiSi alloys using the replica technique under symmetrical tensile-compression loading, and rotational-bending loading were carried out with the same nominal stress amplitude. Observation and analysis results indicate that under different load types, the cracks display a trend of slow initiation growth and then rapid growth. The critical point is identified at the approximate value of 0.8 of the fatigue life fraction, and the crack growth rate of the sample under tensile-compression load is approximately an order of magnitude higher than that under rotational-bending load, resulting in the average life of the former being significantly shorter than the latter. Combining the observation results of the fractographical analysis and the surface-etched sample replica film, it can be seen that whether it is a tensile-compression load or a rotational-bending load, cracks mainly propagate in intergranular mode after initiation.
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http://dx.doi.org/10.3390/ma13102228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287838PMC
May 2020

Comparative Study of Steel-FRP, FRP and Steel-Reinforced Coral Concrete Beams in Their Flexural Performance.

Materials (Basel) 2020 May 1;13(9). Epub 2020 May 1.

College of Civil Engineering and Architecture, Guilin University of Technology, Guilin 541004, China.

In this study, a comparative study of carbon fiber reinforced polymer (CFRP) bar and steel-carbon fiber composite bar (SCFCB) reinforced coral concrete beams was made through a series of experimental tests and theoretical analyses. The flexural capacity, crack development and failure modes of CFRP and SCFCB-reinforced coral concrete were investigated in detail. They were also compared to ordinary steel-reinforced coral concrete beams. The results show that under the same conditions of reinforcement ratios, the SCFCB-reinforced beams exhibit better performance than CFRP-reinforced beams, and stiffness is slightly lower than that of steel-reinforced beams. Under the same load conditions, the crack width of SCFCB beams was between that of steel-reinforced beams and CFRP bar-reinforced beams. Before the steel core yields, the crack growth rate of SCFCB beam is similar to the steel-reinforced beams. SCFCB has a higher strength utilization rate-about 70-85% of its ultimate strength. Current design guidance was also examined based on the test results. It was found that the existing design specifications for FRP-reinforced normal concrete is not suitable for SCFCB-reinforced coral concrete structures.
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http://dx.doi.org/10.3390/ma13092097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254388PMC
May 2020

Myc-Miz1 signaling promotes self-renewal of leukemia stem cells by repressing Cebpα and Cebpδ.

Blood 2020 04;135(14):1133-1145

Department of Biology, College of Life Sciences, Shanghai Normal University, Shanghai, People's Republic of China.

c-Myc (Myc hereafter) is found to be deregulated and/or amplified in most acute myeloid leukemias (AMLs). Almost all AML cells are dependent upon Myc for their proliferation and survival. Thus, Myc has been proposed as a critical anti-AML target. Myc has Max-mediated transactivational and Myc-interacting zinc finger protein 1 (Miz1)-mediated transrepressional activities. The role of Myc-Max-mediated transactivation in the pathogenesis of AML has been well studied; however, the role of Myc-Miz1-mediated transrepression in AML is still somewhat obscure. Myc protein harboring a V394D mutation (MycV394D) is a mutant form of Myc that lacks transrepressional activity due to a defect in its ability to interact with Miz1. We found that, compared with Myc, the oncogenic function of MycV394D is significantly impaired. The AML/myeloproliferative disorder that develops in mice receiving MycV394D-transduced hematopoietic stem/progenitor cells (HSPCs) is significantly delayed compared with mice receiving Myc-transduced HSPCs. Using a murine MLL-AF9 AML model, we found that AML cells expressing MycV394D (intrinsic Myc deleted) are partially differentiated and show reductions in both colony-forming ability in vitro and leukemogenic capacity in vivo. The reduced frequency of leukemia stem cells (LSCs) among MycV394D-AML cells and their reduced leukemogenic capacity during serial transplantation suggest that Myc-Miz1 interaction is required for the self-renewal of LSCs. In addition, we found that MycV394D-AML cells are more sensitive to chemotherapy than are Myc-AML cells. Mechanistically, we found that Myc represses Miz1-mediated expression of CCAAT/enhancer-binding protein α (Cebpα) and Cebpδ, thus playing an important role in the pathogenesis of AML by maintaining the undifferentiated state and self-renewal capacity of LSCs.
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http://dx.doi.org/10.1182/blood.2019001863DOI Listing
April 2020

Comparative proteomic analysis reveals that exogenous 6-benzyladenine (6-BA) improves the defense system activity of waterlogged summer maize.

BMC Plant Biol 2020 Jan 29;20(1):44. Epub 2020 Jan 29.

State Key Laboratory of Crop Biology and College of Agronomy, Shandong Agricultural University, Taian, Shandong, 271018, People's Republic of China.

Background: Exogenous 6-benzyladenine (6-BA) could improve leaf defense system activity. In order to better understand the regulation mechanism of exogenous 6-benzyladenine (6-BA) on waterlogged summer maize, three treatments including control (CK), waterlogging at the third leaf stage for 6 days (V3-6), and application of 100 mg dm 6-BA after waterlogging for 6 days (V3-6-B), were employed using summer maize hybrid DengHai 605 (DH605) as the experimental material. We used a labeling liquid chromatography-based quantitative proteomics approach with tandem mass tags to determine the changes in leaf protein abundance level at the tasseling stage.

Results: Waterlogging significantly hindered plant growth and decreased the activities of SOD, POD and CAT. In addition, the activity of LOX was significantly increased after waterlogging. As a result, the content of MDA and HO was significantly increased which incurred serious damages on cell membrane and cellular metabolism of summer maize. And, the leaf emergence rate, plant height and grain yield were significantly decreased by waterlogging. However, application of 6-BA effectively mitigated these adverse effects induced by waterlogging. Compared with V3-6, SOD, POD and CAT activity of V3-6-B were increased by 6.9, 12.4, and 18.5%, LOX were decreased by 13.6%. As a consequence, the contents of MDA and HO in V3-6-B were decreased by 22.1 and 17.2%, respectively, compared to that of V3-6. In addition, the leaf emergence rate, plant height and grain yield were significantly increased by application of 6-BA. Based on proteomics profiling, the proteins involved in protein metabolism, ROS scavenging and fatty acid metabolism were significantly regulated by 6-BA, which suggested that application of 6-BA exaggerated the defensive response of summer maize at proteomic level.

Conclusions: These results demonstrated that 6-BA had contrastive effects on waterlogged summer maize. By regulating key proteins related to ROS scavenging and fatty acid metabolism, 6-BA effectively increased the defense system activity of waterlogged summer maize, then balanced the protein metabolism and improved the plant physiological traits and grain yield.
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http://dx.doi.org/10.1186/s12870-020-2261-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988316PMC
January 2020

Diagnostic accuracy of urinary survivin mRNA expression detected by RT-PCR compared with urine cytology in the detection of bladder cancer: A meta-analysis of diagnostic test accuracy in head-to-head studies.

Oncol Lett 2020 Feb 18;19(2):1165-1174. Epub 2019 Dec 18.

Clinical Laboratory, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, P.R. China.

Survivin is a promising marker for the diagnosis of bladder cancer. The accuracy and clinical value of urinary survivin mRNA expression were compared with urine cytology, which is the standard diagnostic method for bladder cancer. Scientific databases, including PubMed, Web of Science, Cochrane Library and China National Knowledge Infrastructure, were searched in order to find studies that examined urinary survivin mRNA expression and urine cytology in the diagnosis of bladder cancer. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool in Revman 5.3 and data analysis was conducted using Stata/MP. The I statistic was used to evaluate heterogeneity and Deeks' funnel plot was generated to assess the possibility of publication bias. A total of 15 studies that evaluated a total of 1,624 patients were included in the present meta-analysis. The pooled sensitivity and specificity values for the detection of urinary survivin mRNA expression in the diagnosis of bladder cancer were 0.86 [95% confidence interval (CI), 0.81-0.90] and 0.95 (95% CI, 0.93-0.96), respectively. Regarding urine cytology, the pooled sensitivity and specificity values were 0.42 (95% CI, 0.36-0.48) and 1.00 (95% CI, 0.98-1.00), respectively. Furthermore, the differences in pooled sensitivity were statistically significant in the diagnosis of grade 1 and 2 bladder tumors. Summary receiver operating characteristic curve values for urinary survivin mRNA expression and urine cytology were 0.95 (95% CI, 0.93-0.97) and 0.86 (95% CI, 0.83-0.89), respectively. Urinary survivin mRNA expression was also more accurate compared with other diagnostic indicators, including positive likelihood ratios, negative likelihood ratios, diagnostic odds ratios and Youden's index. Compared with traditional urine cytology, urinary survivin mRNA detection using reverse transcription-PCR was identified to be more effective in the diagnosis of early bladder cancer.
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http://dx.doi.org/10.3892/ol.2019.11227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955656PMC
February 2020

Corrigendum to "Compatibility of chlorantraniliprole with the generalist predator Coccinella septempunctata L. (Coleoptera: Coccinellidae) based toxicity, life-cycle development and population parameters in laboratory microcosms" [225 (2019) 182-190].

Chemosphere 2020 Apr 9;245:125633. Epub 2020 Jan 9.

Key Laboratory of Pesticide Toxicology and Application Technique, College of Plant Protection, Shandong Agricultural University, Tai'an, Shandong, 271018, China; Research Center of Pesticide Environmental Toxicology, Shandong Agricultural University, Tai'an, Shandong, 271018, China. Electronic address:

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http://dx.doi.org/10.1016/j.chemosphere.2019.125633DOI Listing
April 2020
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