Active oxygen species mediate the iron-promoting electrocatalysis of oxygen evolution reaction on metal oxyhydroxides.

Iron is an extraordinary promoter to impose nickel/cobalt (hydr)oxides as the most active oxygen evolution reaction catalysts, whereas the synergistic effect is actively debated. Here, we unveil that active oxygen species mediate a strong electrochemical interaction between iron oxides (FeOxHy) and the supporting metal oxyhydroxides. Our survey on the electrochemical behavior of nine supporting metal oxyhydroxides (M(O)OH) uncovers that FeOxHy synergistically promotes substrates that can produce active oxygen species exclusively. Tafel slopes correlate with the presence and kind of oxygen species. Moreover, the oxygen evolution reaction onset potentials of FeOxHy@M(O)OH coincide with the emerging potentials of active oxygen species, whereas large potential gaps are present for intact M(O)OH. Chemical probe experiments suggest that active oxygen species could act as proton acceptors and/or mediators for proton transfer and/or diffusion in cooperative catalysis. This discovery offers a new insight to understand the synergistic catalysis of Fe-based oxygen evolution reaction electrocatalysts.

The miR-141/200c-STAT4 Axis Contributes to Leukemogenesis by Enhancing Cell Proliferation in T-PLL.

T-prolymphocytic leukemia (T-PLL) is a rare and mature T-cell malignancy with characteristic chemotherapy-refractory behavior and a poor prognosis. Molecular concepts of disease development have been restricted to protein-coding genes. Recent global microRNA (miR) expression profiles revealed miR-141-3p and miR-200c-3p (miR-141/200c) as two of the highest differentially expressed miRs in T-PLL cells versus healthy donor-derived T cells. Furthermore, miR-141/200c expression separates T-PLL cases into two subgroups with high and low expression, respectively. Evaluating the potential pro-oncogenic function of miR-141/200c deregulation, we discovered accelerated proliferation and reduced stress-induced cell death induction upon stable miR-141/200c overexpression in mature T-cell leukemia/lymphoma lines. We further characterized a miR-141/200c-specific transcriptome involving the altered expression of genes associated with enhanced cell cycle transition, impaired DNA damage responses, and augmented survival signaling pathways. Among those genes, we identified STAT4 as a potential miR-141/200c target. Low STAT4 expression (in the absence of miR-141/200c upregulation) was associated with an immature phenotype of primary T-PLL cells as well as with a shortened overall survival of T-PLL patients. Overall, we demonstrate an aberrant miR-141/200c-STAT4 axis, showing for the first time the potential pathogenetic implications of a miR cluster, as well as of STAT4, in the leukemogenesis of this orphan disease.

Effect of Transport Properties of Crystalline Transition Metal (Oxy)hydroxides on Oxygen Evolution Reaction.

Electronic transport plays a pivotal role in the electrolysis of semiconducting electrocatalysts for oxygen evolution reaction (OER), while it is mostly underestimated and largely unexplored. Here, by investigating the electronic transport behavior of seven archetypical crystalline Co/Ni/Fe-based (oxy)hydroxides (unary, binary, and ternary) under OER potential, we study how and the extent to which it affects the apparent catalytic performances. The electronic transports of unary metal (oxy)hydroxides follow the order of Co > Ni > Fe, and their binary or ternary compounds can generally impose one order of magnitude higher electrical conductivity. By studying the dependence of catalytic performances on electrical conductivities, we further unveil that charge transportability not only determines the electronic accessibility of catalytic nanoparticles but also, to our surprise, regulates the reaction kinetics of the electronically accessible active sites. Remarkably, the regulation extent of reaction kinetics correlates with the electrical conductivities of electrocatalysts, suggesting that the electrocatalytic process is strongly coupled with electronic transport. The work presents an overview of electronic transports of crystalline (oxy)hydroxides under OER potentials and highlights their pivotal role in unfolding catalytic potential, holding both fundamental and technical implications for the screen and design of efficient electrocatalysts.

Oncogenic role and target properties of the lysine-specific demethylase KDM1A in chronic lymphocytic leukemia.

In chronic lymphocytic leukemia (CLL), epigenetic alterations are considered to centrally shape the transcriptional signatures that drive disease evolution and underlie its biological and clinical subsets. Characterizations of epigenetic regulators, particularly histone-modifying enzymes, are very rudimentary in CLL. In efforts to establish effectors of the CLL-associated oncogene T-cell leukemia 1A (TCL1A), we identified here the lysine-specific histone demethylase KDM1A to interact with the TCL1A protein in B cells in conjunction with an increased catalytic activity of KDM1A. We demonstrate that KDM1A is upregulated in malignant B cells. Elevated KDM1A and associated gene expression signatures correlated with aggressive disease features and adverse clinical outcomes in a large prospective CLL trial cohort. Genetic Kdm1a knockdown in Eµ-TCL1A mice reduced leukemic burden and prolonged animal survival, accompanied by upregulated p53 and proapoptotic pathways. Genetic KDM1A depletion also affected milieu components (T, stromal, and monocytic cells), resulting in significant reductions in their capacity to support CLL-cell survival and proliferation. Integrated analyses of differential global transcriptomes (RNA sequencing) and H3K4me3 marks (chromatin immunoprecipitation sequencing) in Eµ-TCL1A vs iKdm1aKD;Eµ-TCL1A mice (confirmed in human CLL) implicate KDM1A as an oncogenic transcriptional repressor in CLL which alters histone methylation patterns with pronounced effects on defined cell death and motility pathways. Finally, pharmacologic KDM1A inhibition altered H3K4/9 target methylation and revealed marked anti-B-cell leukemic synergisms. Overall, we established the pathogenic role and effector networks of KDM1A in CLL via tumor-cell intrinsic mechanisms and its impacts in cells of the microenvironment. Our data also provide rationales to further investigate therapeutic KDM1A targeting in CLL.

The proto-oncogene TCL1A deregulates cell cycle and genomic stability in CLL.

Upregulation of the proto-oncogene T-cell leukemia/lymphoma 1A (TCL1A) is causally implicated in various B-cell and T-cell malignancies. High-level TCL1A correlates with aggressive disease features and inferior clinical outcomes. However, the molecular and cell biological consequences of, particularly nuclear, TCL1A are not fully elucidated. We observed here in mouse models of subcellular site-specific TCL1A-induced lymphomagenesis that TCL1A exerts a strong transforming impact via nuclear topography. In proteomic screens of TCL1A-bound molecules in chronic lymphocytic leukemia (CLL) cells and B-cell lymphoma lines, we identified regulators of cell cycle and DNA repair pathways as novel TCL1A interactors, particularly enriched under induced DNA damage and mitosis. By functional mapping and in silico modeling, we specifically identified the mitotic checkpoint protein, cell division cycle 20 (CDC20), as a direct TCL1A interactor. According to the regulatory impact of TCL1A on the activity of the CDC20-containing mitotic checkpoint and anaphase-promoting complexes during mitotic progression, TCL1A overexpression accelerated cell cycle transition in B-cell lymphoma lines, impaired apoptotic damage responses in association with pronounced chromosome missegregation, and caused cellular aneuploidy in Eµ-TCL1A mice. Among hematopoietic cancers, CDC20 levels seem particularly low in CLL. CDC20 expression negatively correlated with TCL1A and lower expression marked more aggressive and genomically instable disease and cellular phenotypes. Knockdown of Cdc20 in TCL1A-initiated murine CLL promoted aneuploidy and leukemic acceleration. Taken together, we discovered a novel cell cycle-associated effect of TCL1A abrogating controlled cell cycle transition. This adds to our concept of oncogenic TCL1A by targeting genome stability. Overall, we propose that TCL1A acts as a pleiotropic adapter molecule with a synergistic net effect of multiple hijacked pathways.

Identifying the geometric catalytic active sites of crystalline cobalt oxyhydroxides for oxygen evolution reaction.

Unraveling the precise location and nature of active sites is of paramount significance for the understanding of the catalytic mechanism and the rational design of efficient electrocatalysts. Here, we use well-defined crystalline cobalt oxyhydroxides CoOOH nanorods and nanosheets as model catalysts to investigate the geometric catalytic active sites. The morphology-dependent analysis reveals a ~50 times higher specific activity of CoOOH nanorods than that of CoOOH nanosheets. Furthermore, we disclose a linear correlation of catalytic activities with their lateral surface areas, suggesting that the active sites are exclusively located at lateral facets rather than basal facets. Theoretical calculations show that the coordinatively unsaturated cobalt sites of lateral facets upshift the O 2p-band center closer to the Fermi level, thereby enhancing the covalency of Co-O bonds to yield the reactivity. This work elucidates the geometrical catalytic active sites and enlightens the design strategy of surface engineering for efficient OER catalysts.

The Modes of Dysregulation of the Proto-Oncogene T-Cell Leukemia/Lymphoma 1A.

Incomplete biological concepts in lymphoid neoplasms still dictate to a large extent the limited availability of efficient targeted treatments, which entertains the mostly unsatisfactory clinical outcomes. Aberrant expression of the embryonal and lymphatic TCL1 family of oncogenes, i.e., the paradigmatic TCL1A, but also TML1 or MTCP1, is causally implicated in T- and B-lymphocyte transformation. TCL1A also carries prognostic information in these particular T-cell and B-cell tumors. More recently, the TCL1A oncogene has been observed also in epithelial tumors as part of oncofetal stemness signatures. Although the concepts on the modes of TCL1A dysregulation in lymphatic neoplasms and solid tumors are still incomplete, there are recent advances in defining the mechanisms of its (de)regulation. This review presents a comprehensive overview of TCL1A expression in tumors and the current understanding of its (dys)regulation via genomic aberrations, epigenetic modifications, or deregulation of TCL1A-targeting micro RNAs. We also summarize triggers that act through such transcriptional and translational regulation, i.e., altered signals by the tumor microenvironment. A refined mechanistic understanding of these modes of dysregulations together with improved concepts of TCL1A-associated malignant transformation can benefit future approaches to specifically interfere in TCL1A-initiated or -driven tumorigenesis.

Complete plastome sequence of Macaranga tanarius (L.) Muell. Arg. (Euphorbiaceae): a fast-growing timber species.

Macaranga tanarius (L.) Muell. Arg. is a tree species within Euphorbiaceae, which can be used for building timber and its extract can be used to treat diabetes. In this report, we describe the complete plastome sequence of Macaranga tanarius. The complete plastome of Macaranga tanarius (L.) Muell. Arg. is of 165,362 bp in length, and it is with typical plastome structure and gene content of angiosperm plastome, including two reverse repeat regions (IRs) of 27,503 bp, large single copy region (LSC) of 91,443 bp, and small single copy (SSC) region of 18,913 bp. The plastome contains 131 genes, including 85 protein coding genes, 38 tRNA genes, eight rRNA genes (i.e., 5S rRNA, 4.5S rRNA, 16S rRNA, and 23S rRNA). The total G/C content of Macaranga tanarius (L.) Muell. Arg.plastome is 35.6%. The complete plastome sequence is conducive to the development and utilization of Euphorbiaceae resources and the phylogenetic study.

A Solid-State Electrochemical Sensor for Determination of Effective Acidity of Aqueous Solutions with High Acidity / 分析化学

A new all-solid state electrode modified with poly ( o-aminophenol-co-o-phenylenediamine ) film was prepared by cyclic voltammetry.The electrochemical response of the electrode to various solutions in the available acidity range of 1.00 × 10-12-10.0 mol/L was studied by cyclic voltammetry.The results showed that the reduction peak potentials and the available acidity of solution showed good linear relationship in 3 stages of 1.00×10-10-0.10 mol/L, 0.10-2.00 mol/L and 2.00-10.0 mol/L respectively, and the regression equations were Epc=0.0456lgC(H+)-0.295, Epc=0.0803c(H+)-0.309, and Epc=0.0278c(H+)-0.188, respectively.There were similar responses in the solutions of H2 SO4 , HNO3 and HClO4 in the concentration range of 1.00-8.00 mol/L.The preparation method of electrode was simple, and the determination range of available acidity was as wide as 1.0 ×10-10-10.0 mol/L, which laid the foundation for the development of solid-state electrochemical sensors for determination of acidity of high acidity solution.

Paraneoplastic pemphigus associated with chronic lymphocytic leukemia: A case report.

RATIONALE: Paraneoplastic pemphigus (PNP) is an autoimmune syndrome associated with neoplasms. The treatment approach principally includes suppressing the immunity, but its therapeutic effect is not satisfying. PATIENT CONCERNS: We report a case of paraneoplastic pemphigus linked to chronic lymphocytic leukemia in a 63-year-old man. DIAGNOSES: At first, the patient was diagnosed with pityriasis rose caused by a viral infection. Biopsies for histology and immunofluorescence showed PNP, was treated with immunosuppressive and antiinfective therapy. INTERVENTIONS: Immunosuppressive and antiinfective therapy were performed. OUTCOMES: The skin lesions of PNP were alleviated. However, the infections were aggravated and the disease progressed. The patient died of respiratory failure. LESSONS: Treatment for PNP should be adapted to disease severity as early as possible. Antiinfection treatment should be timely and effective because infections are the most common complication that can lead to death.