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Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155986/1/art41237.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155986/2/art41237_am.pd

High‐Density Lipoprotein in Lupus: Disease Biomarkers and Potential Therapeutic Strategy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152788/1/art41059_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152788/2/art41059.pd

Lipophilic M(α,α′-OC5H11)8phthalocyanines (M = H2 and Ni(II)): synthesis, electronic structure, and their utility for highly efficient carbonyl reductions

A lipophilic and electron-rich phthalocyanine (α,α′-n-OC5H11)8-H2Pc and its nickel(II) complex (α,α′-n-OC5H11)8-Ni(II)Pc have been synthesized and characterized. Detailed analyses of the electronic structure were carried out by spectroscopy, electrochemistry, spectroelectrochemistry, and TD-DFT calculations. A series of experiments demonstrate that the (α,α′-n-OC5H11)8-Ni(II)Pc complex can be used as a catalyst for highly efficient carbonyl reductions.Original publication is available at http://dx.doi.org/10.1039/C5DT03256

Enantioselective electrochemical carbon-chloride bond cleavage of hexachlorocyclohexanes (HCHs) catalyzed by Mn (III) Cl-phthalocyanine

A lipophilic and electron-rich metallophthalocyanine Mn(III)Cl(α,α′-n-OC5H11)8Pc has been synthesized and characterized. A series of electrochemical experiments demonstrate that the Mn(III)Cl(α,α′-n-OC5H11)8Pc complex can be used as a catalyst for highly efficient carbon-chloride bond cleavage of environmental toxic hexachlorocyclohexanes (HCHs) through electrochemical catalysis, and that the increased catalytic efficiency is related to the enantiomeric carbon-chloride σ-bond of HCHs

Battle of GLP-1 delivery technologies

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) belong to an important therapeutic class for treatment of type 2 diabetes. Six GLP-1 RAs, each utilizing a unique drug delivery strategy, are now approved by the Food and Drug Administration (FDA) and additional, novel GLP-1 RAs are still under development, making for a crowded marketplace and fierce competition among the manufacturers of these products. As rapid elimination is a major challenge for clinical application of GLP-1 RAs, various half-life extension strategies have been successfully employed including sequential modification, attachment of fatty-acid to peptide, fusion with human serum albu- min, fusion with the fragment crystallizable (Fc) region of a monoclonal antibody, sustained drug delivery sys- tems, and PEGylation. In this review, we discuss the scientific rationale of the various half-life extension strategies used for GLP-1 RA development. By analyzing and comparing different approved GLP-1 RAs and those in development, we focus on assessing how half-life extending strategies impact the pharmacokinetics, pharmacodynamics, safety, patient usability and ultimately, the commercial success of GLP-1 RA products. We also anticipate future GLP-1 RA development trends. Since similar drug delivery strategies are also applied for de- veloping other therapeutic peptides, we expect this case study of GLP-1 RAs will provide generalizable concepts for the rational design of therapeutic peptides products with extended duration of action

Enantioselective electrochemical carbon-chloride bond cleavage of hexachlorocyclohexanes (HCHs) catalyzed by Mn (III) Cl-phthalocyanine

A lipophilic and electron-rich metallophthalocyanine Mn(III)Cl(α,α′-n-OC5H11)8Pc has been synthesized and characterized. A series of electrochemical experiments demonstrate that the Mn(III)Cl(α,α′-n-OC5H11)8Pc complex can be used as a catalyst for highly efficient carbon-chloride bond cleavage of environmental toxic hexachlorocyclohexanes (HCHs) through electrochemical catalysis, and that the increased catalytic efficiency is related to the enantiomeric carbon-chloride σ-bond of HCHs

Facile synthesis, spectroscopic and electrochemical properties, and theoretical calculations of porphyrin dimers with a bridging amide-bonded xanthene moiety

A free base porphyrin dimer bridged by a flexible amide-bonded xanthene moiety and its binuclear zinc(II) complex zinc(II) complex were synthesized and characterized. Structural characterization by MS and 1H NMR spectroscopy confirmed the bridged porphyrin dimer structure. The properties of the dimers were characterized by IR, UV-visible absorption, fluorescence and magnetic circular dichroism (MCD) spectroscopy, and electrochemistry studies. Theoretical calculations were carried out to analyze the electronic structures of porphyrin dimers with a bridging amide-bonded xanthene moiety

ZEB1 Is a Transcription Factor That Is Prognostic and Predictive in Diffuse Gliomas

Objective: To address the unmet medical need to better prognosticate patients with diffuse gliomas and to predict responses to chemotherapy regimens.Methods: ZEB1 alterations were retrospectively identified from a cohort of 1,160 diffuse glioma patients. Epigenome-wide association scans (EWAS) were performed on available data. We determined the utility of ZEB1 as a prognostic indicator of patient survival in diffuse gliomas and assessed the value of ZEB1 to predict the efficacy of treating diffuse glioma patients with procarbazine, CCNU, and vincristine along with radiation at diagnosis. Decision curve analysis (DCA) was used to determine if ZEB1 added benefit to clinical decision-making over and above conventional methods.Results: Fifteen percent of diffuse glioma patients had a ZEB1 deletion. ZEB1 deletion was associated with poor overall survival (OS) with and without adjustment for age and tumor grade (adjusted HR: 4.25; 95% CI: 2.35 to 7.66; P < 0.001). Decision curve analysis confirmed that ZEB1 status with or without IDH1 was more beneficial to clinical decision making than conventional information such as age and tumor grade. We showed that ZEB1 regulates TERT expression, and patients with ZEB1 deletions likely subsume patients with mutant TERT expression in diffuse gliomas. ZEB1 influenced clinical decision making to initiate procarbazine, CCNU, and vincristine treatment.Conclusion: We demonstrate the prognostic value of ZEB1 in diffuse glioma patients. We further determine ZEB1 to be a vital and influential molecular marker in clinical decisions that exceed conventional methods regarding whether to treat or not treat patients with diffuse glioma

Beclin1 Controls the Levels of p53 by Regulating the Deubiquitination Activity of USP10 and USP13

Autophagy is an important intracellular catabolic mechanism that mediates the degradation of cytoplasmic proteins and organelles. We report a potent small molecule inhibitor of autophagy named “spautin-1” for specific and potent autophagy inhibitor-1. Spautin-1 promotes the degradation of Vps34 PI3 kinase complexes by inhibiting two ubiquitin-specific peptidases, USP10 and USP13, that target the Beclin1 subunit of Vps34 complexes. Beclin1 is a tumor suppressor and frequently monoallelically lost in human cancers. Interestingly, Beclin1 also controls the protein stabilities of USP10 and USP13 by regulating their deubiquitinating activities. Since USP10 mediates the deubiquitination of p53, regulating deubiquitination activity of USP10 and USP13 by Beclin1 provides a mechanism for Beclin1 to control the levels of p53. Our study provides a molecular mechanism involving protein deubiquitination that connects two important tumor suppressors, p53 and Beclin1, and a potent small molecule inhibitor of autophagy as a possible lead compound for developing anticancer drugs

The Development of English and Chinese Oral Language through Drawing for Primary Grade Students

This research explored how the drawings of five-to seven-year-old children reflect their interests and emotions. This research also evaluated the role these drawings played in their literacy education and development. Two groups of students were compared in regards to the impact drawing had on their literacy development. The experimental group received the drawing intervention while the control group received literacy instruction only. Teachers were interviewed to ascertain whether the intervention affected the students’ literacy development, as well as to gain insight into children’s thinking emanating from their drawings. It was found that the students who used drawing as a complement to their study increased comprehension and retention of the material more than students who did not include drawing as a part of their studies. The results of this research showed that drawing may assist children’s oral expression of literature comprehension and may also help their memory